Cholesterol is easily oxidized and can be transformed into numerous oxidation products, among which oxysterols. Phytosterols are plant sterols related to cholesterol. Both oxysterols and phytosterols can have an impact on human health and diseases.Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. On the other hand, phytosterols are plant-derived compounds structurally related to cholesterol, which can also have an impact on human health. Here, we review the current knowledge about the role of oxysterols and phytosterols on human health and focus on the impact of their pathways on diseases of the central nervous system (CNS), autoimmune diseases, including inflammatory bowel diseases (IBD), vascular diseases, and cancer in both experimental models and human studies. We will first discuss the implications of oxysterols and then of phytosterols in different human diseases.