Cells have different sets of molecules for performing an array of physiological functions.Nu-cleic acids have stored and carried the information throughout evolution,whereas proteins have been attributed to performing most of the cellular functions.To perform these functions,proteins need to have a unique conformation and a definite lifespan.These attributes are achieved by a highly coordinated pro-tein quality control (PQC) system comprising chaperones to fold the proteins in a proper three-dimensional structure,ubiquitin-proteasome system for selective degradation of proteins,and autophagy for bulk clearance of cell debris.Many kinds of stresses and perturbations may lead to the weakening of these protective cellular machinery,leading to the unfolding and aggregation of cellular proteins and the occurrence of numerous pathological conditions.However,modulating the expression and functional ef-ficiency of molecular chaperones,E3 ubiquitin ligases,and autophagic proteins may diminish cellular proteotoxic load and mitigate various pathological effects.Natural medicine and small molecule-based therapies have been well-documented for their effectiveness in modulating these pathways and reestab-lishing the lost proteostasis inside the cells to combat disease conditions.The present article summarizes various similar reports and highlights the importance of the molecules obtained from natural sources in disease therapeutics.