Skin is the largest organ of human body which is consistently exposed to various abiotic factors. Among all the environmental factors, ultraviolet radiation (UVR) is the major concern for many skin-related diseases. Induction of melanin synthesis plays a significant role in overcoming the hazardous effects of intensive irradiation. Human tyrosinase related proteins (TYRP1) are responsible for the melanin synthesis that imparts color to the skin, eye, and hair. However, excessive amount of melanin production leads to the development of many life-threatening diseases including hyperpigmentation and neurodegenerative disorders. Inhibition of this enzyme has become one of the influencing strategies to balance the biosynthesis of melanin and play a major role in the treatment of skin-related diseases. There are several synthetic and semi-synthetic drugs available in the market which causes deleterious and life threatening side effects on human skin. Recent trends suggest the use of eco-friendly UV-absorbing compounds as natural sunscreens. We have used 06 UV-absorbing compounds with reference commercial sunscreen ingredient such as kojic acid (KOJ) and hydroquinone (HYD) for searching novel inhibitory activity of TYRP1 by molecular docking, drug likeness and ADMET approach. Among the 06 compounds, palythene (PAE) had effective binding affinity, bioavailability, and drug likeness properties with highest binding energy (-7.37 kcal/mol) as compared to KOJ (-5.19) and HYD (-4.37). The potent inhibitory activity of PAE over TYRP1 enzyme can be used for the development of highly effective commercial eco-friendly anti-melanogenic fairness sunscreen products for the skin related diseases.