Lead poisoning is a major public health issue, particularly in developing countries. Despite efforts to control lead exposure, cases of lead poisoning continue to occur. Lead exposure causes harmful effects on the hematopoietic, renal, reproductive, and central nervous systems, primarily through increased oxidative stress. Modulation of cellular thiols has been used as a therapeutic strategy against lead poisoning. Various antioxidants, including N-acetylcysteine, α-lipoic acid, vitamin E, quercetin, and herbal extracts, have shown protective effects against lead-induced injury. This review discusses recent updates on the health effects of lead exposure, relevant biomarkers, and mechanisms of lead toxicity. It also covers recent advances in chelation therapy and new therapeutic strategies, such as nanoencapsulation, for treating lead-induced toxic manifestations. Lead affects the nervous system, causing encephalopathy, irritability, poor attention span, headaches, muscular tremor, memory loss, and hallucinations. It also causes peripheral neuropathy, characterized by reduced motor activity due to loss of myelin sheath. Lead affects the hematopoietic system by inhibiting hemoglobin synthesis and reducing the lifespan of erythrocytes. Lead poisoning can cause hemolytic anemia and frank anemia. Lead inhibits key enzymes in the heme synthesis pathway, leading to anemia. Lead also affects the kidneys, causing renal dysfunction, and the cardiovascular system, leading to hypertension and cardiovascular disease. Lead causes reproductive health issues, including infertility, miscarriage, and pre-eclampsia. Lead is stored in bones and can be released into the bloodstream, especially during bone remodeling. Lead toxicity is primarily due to oxidative stress, which results from the generation of reactive oxygen species (ROS) and depletion of antioxidant reserves. Lead can substitute for other cations, affecting various biological processes. Antioxidants, such as vitamins B, C, and E, and flavonoids, play a crucial role in protecting against lead-induced oxidative stress. Natural antioxidants, including vitamins, flavonoids, and herbal compounds, have been shown to prevent and treat lead-induced toxicity. Recent strategies, such as nanoencapsulation and liposome-mediated drug delivery, aim to improve the bioavailability of antioxidants for effective treatment of lead toxicity.Lead poisoning is a major public health issue, particularly in developing countries. Despite efforts to control lead exposure, cases of lead poisoning continue to occur. Lead exposure causes harmful effects on the hematopoietic, renal, reproductive, and central nervous systems, primarily through increased oxidative stress. Modulation of cellular thiols has been used as a therapeutic strategy against lead poisoning. Various antioxidants, including N-acetylcysteine, α-lipoic acid, vitamin E, quercetin, and herbal extracts, have shown protective effects against lead-induced injury. This review discusses recent updates on the health effects of lead exposure, relevant biomarkers, and mechanisms of lead toxicity. It also covers recent advances in chelation therapy and new therapeutic strategies, such as nanoencapsulation, for treating lead-induced toxic manifestations. Lead affects the nervous system, causing encephalopathy, irritability, poor attention span, headaches, muscular tremor, memory loss, and hallucinations. It also causes peripheral neuropathy, characterized by reduced motor activity due to loss of myelin sheath. Lead affects the hematopoietic system by inhibiting hemoglobin synthesis and reducing the lifespan of erythrocytes. Lead poisoning can cause hemolytic anemia and frank anemia. Lead inhibits key enzymes in the heme synthesis pathway, leading to anemia. Lead also affects the kidneys, causing renal dysfunction, and the cardiovascular system, leading to hypertension and cardiovascular disease. Lead causes reproductive health issues, including infertility, miscarriage, and pre-eclampsia. Lead is stored in bones and can be released into the bloodstream, especially during bone remodeling. Lead toxicity is primarily due to oxidative stress, which results from the generation of reactive oxygen species (ROS) and depletion of antioxidant reserves. Lead can substitute for other cations, affecting various biological processes. Antioxidants, such as vitamins B, C, and E, and flavonoids, play a crucial role in protecting against lead-induced oxidative stress. Natural antioxidants, including vitamins, flavonoids, and herbal compounds, have been shown to prevent and treat lead-induced toxicity. Recent strategies, such as nanoencapsulation and liposome-mediated drug delivery, aim to improve the bioavailability of antioxidants for effective treatment of lead toxicity.