Colonic diseases and disorders necessitate precise drug delivery strategies to optimize therapeutic outcomes while minimizing systemic side effects. This paper explores the multifaceted landscape of colon-specific drug delivery, elucidating various strategies employed to achieve targeted release. We delve into the intricate design principles of prodrugs, pH-responsive formulations, and stimuli-responsive nanocarriers, offering a critical evaluation of their merits and challenges. The efficient delivery of therapeutic agents to the colon has emerged as a pivotal challenge in pharmaceutical research, particularly in the context of treating localized gastrointestinal disorders and enhancing the efficacy of drugs with systemic applications. This review paper aims to provide a comprehensive overview of various colon-targeting strategies employed in drug delivery systems. We systematically analyze and synthesize the current state of knowledge regarding different approaches, including prodrugs, pH-sensitive systems, time-dependent release systems, and microbial-triggered delivery systems.