Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It? Resveratrol (RSV) is a polyphenolic compound with antioxidant, cardioprotective, neuroprotective, anti-inflammatory, and anticancer properties. However, its limited bioavailability and rapid metabolism hinder its clinical application. This review discusses strategies to enhance RSV's bioavailability and therapeutic efficacy, including combination therapies, derivatization, and nanoparticle encapsulation. Combination therapies with established chemotherapeutic drugs, such as oxaliplatin, cisplatin, 5-FU, and doxorubicin, have shown promising therapeutic effects on various cancers. Derivatization of RSV, including hydroxylation, amination, amidation, imidation, methoxylation, prenylation, halogenation, glycosylation, and oligomerization, can improve its bioavailability and therapeutic outcomes. Encapsulation of RSV in nanoparticles enhances its solubility, absorption, and bioavailability, making it more effective for targeted therapy. RSV derivatives such as piceatannol, 4-aminostilbene, pterostilbene, and tetramethoxystilbene have demonstrated enhanced antioxidant, anti-inflammatory, and anticancer activities. Prenylated and halogenated derivatives also show improved biological activities. Oligomerized RSV derivatives have greater scavenging capacity and biological effectiveness. Nanoparticles, including polymer, metal, solid lipid, and other types, have shown promising preclinical results in enhancing RSV's bioavailability and efficacy. Polymer nanoparticles, such as chitosan-pectin, chitosan-alginate, and gelatin, improve RSV's stability and bioavailability. Metal nanoparticles, such as gold nanoparticles, enhance RSV's anticancer effects through photothermal therapy and increased cytotoxicity. This review provides a platform to compare different approaches to enhance RSV's bioavailability and therapeutic efficacy, guiding future research into better treatment options.Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It? Resveratrol (RSV) is a polyphenolic compound with antioxidant, cardioprotective, neuroprotective, anti-inflammatory, and anticancer properties. However, its limited bioavailability and rapid metabolism hinder its clinical application. This review discusses strategies to enhance RSV's bioavailability and therapeutic efficacy, including combination therapies, derivatization, and nanoparticle encapsulation. Combination therapies with established chemotherapeutic drugs, such as oxaliplatin, cisplatin, 5-FU, and doxorubicin, have shown promising therapeutic effects on various cancers. Derivatization of RSV, including hydroxylation, amination, amidation, imidation, methoxylation, prenylation, halogenation, glycosylation, and oligomerization, can improve its bioavailability and therapeutic outcomes. Encapsulation of RSV in nanoparticles enhances its solubility, absorption, and bioavailability, making it more effective for targeted therapy. RSV derivatives such as piceatannol, 4-aminostilbene, pterostilbene, and tetramethoxystilbene have demonstrated enhanced antioxidant, anti-inflammatory, and anticancer activities. Prenylated and halogenated derivatives also show improved biological activities. Oligomerized RSV derivatives have greater scavenging capacity and biological effectiveness. Nanoparticles, including polymer, metal, solid lipid, and other types, have shown promising preclinical results in enhancing RSV's bioavailability and efficacy. Polymer nanoparticles, such as chitosan-pectin, chitosan-alginate, and gelatin, improve RSV's stability and bioavailability. Metal nanoparticles, such as gold nanoparticles, enhance RSV's anticancer effects through photothermal therapy and increased cytotoxicity. This review provides a platform to compare different approaches to enhance RSV's bioavailability and therapeutic efficacy, guiding future research into better treatment options.