Oxindoles have been a rich source of leads in support of drug discovery efforts and many natural product derivatives have gone onto clinical development. Their rich structural and stereochemical characteristics make them valuable as templates for exploring novel molecular diversity. We have focused on the use of multi-component coupling strategies, due to the ease with which the heterocyclic core structures are formed, allowing both the directed synthesis of natural products and the parallel synthesis of analog libraries. A hybrid drug can have two or more partners, which are assembled covalently with or without a linker. Individual partners of the hybrids should act synergistically to improve the desired pharmacological activity and the hybrid design should follow an in-depth knowledge of the merits and drawbacks of individual partnering of drugs/functional entities with a view to improve the pharmacological efficacy and alleviate the toxicity through the new design. Quinolines are an important group of alkaloid natural products, due to their diverse range of biological activity and structural complexity. A similar strategy was employed for the synthesis of quinolines hybrids by variation of the oxindoles and natural terpene as well. We will present how structural hybridization of small molecule oxindoles has emerged as a promising tool to develop new generations of chiral drug candidates.