Astaxanthin (AST) and fucoxanthin (FUC) are natural xanthophylls, having multidirectional activity, including antioxidant, anti-inflammatory, and anticancer. Both compounds also show antimicrobial activity, which is presented in this review article. There are few papers that have presented the antimicrobial activity of AST. Obtained antimicrobial concentrations of AST (200–4000 µg/mL) are much higher than recommended by the European Food Safety Authority for consumption (2 mg daily). Therefore, we suggest that AST is unlikely to be of use in the clinical treatment of infections. Our knowledge about the antimicrobial activity of FUC is better and this compound acts against many bacteria already in low concentrations 10–250 µg/mL. Toxicological studies on animals present the safety of FUC application in doses 200 mg/kg body weight and higher. Taking available research into consideration, a clinical application of FUC as the antimicrobial substance is real and can be successful. However, this aspect requires further investigation. In this review, we also present potential mechanisms of antibacterial activity of carotenoids, to which AST and FUC belong.