Depression is a complex mental health disorder, often involving abnormal emotional regulation and cognitive impairments, marked by high recurrence rates, significant functional impairment, and challenges in achieving clinical remission. Exploring novel therapeutic strategies derived from natural products holds significant clinical value in tackling issues like poor tolerance and withdrawal symptoms linked to traditional antidepressants. Sinomenine (SIN) is a benzylisoquinoline alkaloid extracted from plants like Sinomenium acutum, and its unique anti-inflammatory and immuneregulating properties offer a new approach for treating depressive disorders. Recently, there's been a lot of research on using SIN to treat depression. This article looks at how SIN works as an antidepressant by examining neurotransmitter systems, neuroinflammatory responses, neurotrophic factors, neuroplasticity, and epigenetic regulation, offering a theoretical foundation for further research and the development of new antidepressant drugs, along with insights for clinical use.