BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The disease affects between 1:400 and 1:1000 ratio of the people worldwide. It is caused by the mutated PKD1 and PKD2 genes which encode for the defective polycystins. Polycystins mimic the receptor protein or protein channel and mediate aberrant cell signaling that causes cystic development in the renal parenchyma. The cystic development is driven by the increased cyclic AMP stimulating fluid secretion and infinite cell growth. In recent years, natural product-derived small molecules or drugs targeting specific signaling pathways have caught attention in the drug discovery discipline. The advantages of natural products over synthetic drugs enthusiast researchers to utilize the medicinal benefits in various diseases including ADPKD.CONCLUSION: Overall, this review discusses some of the previously studied and reported natural products and their mechanisms of action which may potentially be redirected into ADPKD.