Quinoline motifs are essential in several pharmacological active heterocyclic compounds due to their various applications in medicinal and industrial chemistry. Furthermore, there are greater societal expectations in the current scenario that synthetic and medicinal chemists should produce greener and more sustainable chemical processes. Therefore, this mini-review article highlights the traditional and green synthetic approaches of quinoline and its analogs, including multicomponent one-pot reactions and solvent-free reaction conditions utilizing microwave and ultraviolet irradiation-promoted synthesis using eco-friendly and safe reusable catalysts, in addition to discussing the medicinal importance of quinoline derivatives such as anticancer, antioxidant, anti-inflammatory, antimalarial, anti-SARS-CoV-2, and antituberculosis activities within the period from 2011 till 2021. Therefore, the quinoline scaffolds signify a unique class of pharmacophores present in various therapeutic agents.