Leprosy remains highly stigmatized in Nigeria, and its social consequences persist despite biomedical advances and institutional efforts. This study investigates the cultural, social and structural drivers of leprosy-related stigma in Niger State and assesses the roles of government agencies, NGOs and community actors in stigma reduction. The theories of stigma, social identity and labeling were employed for the study. Using a mixed-methods design, data were collected from a survey of 360 respondents, 15 key informants and four focus group discussions, analyzed through descriptive statistics, regression and thematic analysis. Findings show that leprosy is perceived as one of the most stigmatized conditions, driven by misconceptions, supernatural attributions and entrenched cultural narratives, leading to human rights violations such as employment discrimination, social exclusion and unequal healthcare treatment. Institutional responses remain fragmented and under-resourced, while community attitudes especially in rural areas reinforce exclusion. The study concludes that effective stigma mitigation requires a culturally grounded, rights-based and multi-sector approach. As such, the study recommends integrating strengthened public health communication, expanded NGO advocacy, improved healthcare training and community-led efforts to challenge harmful beliefs among other recommendations