Leprosy is a chronic infectious disease caused by the Gram-positive Mycobacterium leprae or M. lepromatosis. Leprosy is a significant public health concern in many parts of the world. It remains a persistent global health challenge, particularly in low-resource settings, despite the success of multidrug therapy (MDT) in reducing disease prevalence. The increasing number of drug-resistant case patients, non-adherence to treatment, and the failure of existing regimens to completely eradicate Mycobacterium leprae underscore the pressing need for novel therapeutic research toward effective treatment. In this review, we explore current conventional therapies. This essay critically examines the challenges posed by prolonged treatment regimens and medication resistance. This review also discusses new developments in leprosy treatment, including the study of new chemical entities in preclinical and clinical settings, as well as promising medication prospects. New drug discovery methods, including high-throughput screening, artificial intelligence, and genomics-guided target identification, are also covered. In addition to new drug discovery, innovative drug delivery methods are also crucial for targeting drug delivery, such as transdermal patches, nanocarriers, and long-acting injectables, which are developed with a focus on improving patient adherence, decreasing the frequency of doses, and enhancing therapeutic efficacy. Collectively, these emerging approaches show promise for a shift toward more efficient, targeted, and patient-friendly leprosy treatments, potentially paving the way for the eventual elimination of the disease.