Sinomenine (SIN), an isoquinoline alkaloid derived from the roots and stems of Sinomenium acutum, has been extensively studied for its bioactivities and mechanisms of action. This review summarizes the research advancements in the biological activities and mechanisms of SIN and its derivatives up to November 2023. SIN exhibits a broad spectrum of pharmacological effects, including antitumor, anti-inflammatory, neuroprotective, and immunosuppressive properties. It is particularly effective against breast, lung, liver, and prostate cancers, with IC₅₀ values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, SIN demonstrates anti-inflammatory and analgesic effects via the NF-κB, MAPK, and Nrf2 signaling pathways. It is used in the treatment of rheumatic arthritis and plays a significant role in cardiovascular and cerebrovascular protection, as well as organ protection, through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. The review highlights the potential of SIN-related compounds in clinical applications and the development of medications derived from natural products. Key findings include the antitumor activity of SIN and its derivatives, which inhibit cancer cell proliferation and induce apoptosis through various signaling pathways. The anti-inflammatory and analgesic effects of SIN are mediated by multiple signaling pathways, including NF-κB, MAPK, and Nrf2. The review also discusses combination strategies that enhance the therapeutic effects of SIN with other drugs, as well as the antitumor activity of SIN derivatives. Overall, SIN and its derivatives show significant potential in the treatment of various diseases, including cancer and inflammatory conditions.Sinomenine (SIN), an isoquinoline alkaloid derived from the roots and stems of Sinomenium acutum, has been extensively studied for its bioactivities and mechanisms of action. This review summarizes the research advancements in the biological activities and mechanisms of SIN and its derivatives up to November 2023. SIN exhibits a broad spectrum of pharmacological effects, including antitumor, anti-inflammatory, neuroprotective, and immunosuppressive properties. It is particularly effective against breast, lung, liver, and prostate cancers, with IC₅₀ values of approximately 121.4 nM against PC-3 and DU-145 cells, primarily through the PI3K/Akt/mTOR, NF-κB, MAPK, and JAK/STAT signaling pathways. Additionally, SIN demonstrates anti-inflammatory and analgesic effects via the NF-κB, MAPK, and Nrf2 signaling pathways. It is used in the treatment of rheumatic arthritis and plays a significant role in cardiovascular and cerebrovascular protection, as well as organ protection, through the NF-κB, Nrf2, MAPK, and PI3K/Akt/mTOR signaling pathways. The review highlights the potential of SIN-related compounds in clinical applications and the development of medications derived from natural products. Key findings include the antitumor activity of SIN and its derivatives, which inhibit cancer cell proliferation and induce apoptosis through various signaling pathways. The anti-inflammatory and analgesic effects of SIN are mediated by multiple signaling pathways, including NF-κB, MAPK, and Nrf2. The review also discusses combination strategies that enhance the therapeutic effects of SIN with other drugs, as well as the antitumor activity of SIN derivatives. Overall, SIN and its derivatives show significant potential in the treatment of various diseases, including cancer and inflammatory conditions.