Phytosterols (PS) are biologically active steroidal compounds obtained from plant foods and cholesterol is found in animals. They have a prominent role in reducing the low-density lipoprotein (LDL) cholesterol levels, thus decreasing the risk of many diseases. PSs also have anti-cancer, antioxidant, antiulcer, immunomodulatory, antibacterial, antifungal effects and modulate inflammation by promoting the wound healing and inhibition of platelet aggregation. The most challenging part concerned about phytosterols was bioavailability. Phytosterol’s absorption and the concentration of circulation over the body were lesser in human intestine compared to cholesterol because of its selectivity and return through intestinal transporters. We searched PubMed, Scopus, Embase, Google scholar and major conference proceedings. Sixteen such therapeutically potent plant steroids were studied in this systematic review to assess the bioavailability issues of phytosterols. Swiss ADME web tool that gives free access to a pool of fast yet robust predictive models for physicochemical properties, pharmacokinetics, drug-likeness and medicinal chemistry friendliness was used for the study.