Sinomenine is one of the most widely known alkaloids owing to different therapeutic properties including anti-inflammatory and immunosuppressive activities, as well as the potency in neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Sinomenine has been studied as a potential anti-inflammatory agent through appropriate structural modifications. Recently, a number of such approaches have been attempted in various laboratories with great success. Several series of derivatives have been synthesized with changes at rings A, B, C and D. Herein, we present an up to date review of modifications and bioactivities of important modified derivatives. These studies offer interesting knowledge on the bioactivity and structural specificity of sinomenine, providing better understanding of the structure-activity relationships (SAR) between designing and development of sinomenine derivative with better therapeutic and lower side effects.