•Dietary astaxanthin and its isomers widely exist in nature.•The cis-isomers exhibit greater health benefits.•(3S,3′S) optical configuration of astaxanthin shows higher biological activity.•The cis-, (3S,3′S)-isomers have greater bioavailability than other isomers which is related to intestinal absorption mediated by transporters. Astaxanthin, a xanthophyll carotenoid, has attracted considerable attention owing to its unique molecular structure and excellent antioxidant properties. Due to its structural particularity, it has many geometrical and optical isomers in the diet; Interestingly, the human body has considerable quantity of Z- and optical isomers despite the intake of E- and (3S,3′S) isomers. However, there remains no systematic analysis and summary of astaxanthin and its isomers regarding health benefits and bioavailability. To address this need, this review details the latest research progress of biological activities related to oxidative damage, and these effects are more obvious in Z- and (3S,3′S)-isomers from the existing research. In addition, we outline a comprehensive analysis of the bioavailability of dietary astaxanthin and its isomers from the perspective of transporter-mediated process (e.g. SR-BI, CD36). Further nvestigation of astaxanthin and its isomers is expected to improve human health and promote their applications in future healthcare-related products.