BACKGROUND: In 2019, the Nigerian Ministry of Health published the first operational guidelines for human immunodeficiency virus self-testing (HIVST) to improve access to human immunodeficiency virus (HIV) testing services among undertested populations in the country. Also, as part of the campaign to increase HIV testing services in Nigeria, the Nigerian Ministry of Health developed standard operating procedures for using HIVST kits. AIM: To systematically review the acceptability and strategies for enhancing the uptake of HIVST in Nigeria. METHODS: The systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Different databases were searched to get the necessary materials needed for this review. Standardized forms developed by the authors were used for data extraction to minimize the risk of bias and ensure that the articles used for the study were properly screened. Identified articles were first screened using the titles and their abstracts. The full papers were screened, and the similarities of the documents were determined. Qualitative, quantitative, and mixed-method studies were evaluated using the Critical Appraisal Skills Programme and Critical Appraisal Framework criteria. RESULTS: All the publications reviewed were published between 2015 and 2022, with 33.3% published in 2021. Most (77.8%) of the studies were cross-sectional, 43.3% were conducted in Lagos State, and 26.3% were conducted among young people. The study revealed a high level of acceptability of HIVST. Certain factors, such as gender, sexual activity, and previous testing experience, influence the acceptability of HIV self-testing, with some individuals more likely to opt-out. The cost of the kit was reported as the strongest factor for choosing HIVST services, and this ranged from 200 to 4000 Naira (approximately United States Dollar 0.55-11.07), with the majority willing to pay 500 Naira (approximately United States Dollar 1.38). Privately-owned, registered pharmacies, youth-friendly centres, supermarkets, and online stores were the most cited access locations for HIVST. The least influential attribute was the type of specimen needed for HIVST. Strategies addressing cost and preferred access points and diverse needs for social media promotion, local translation of product use instructions, and HIVST distribution led by key opinion leaders for key populations were found to significantly enhance HIVST uptake and linkage to care. CONCLUSION: HIVST acceptability is generally high from an intention-to-use perspective. Targeted strategies are required to improve the acceptability of HIV self-testing, especially among males, sexually active individuals, and first-time testers. Identified and proposed uptake-enhancing strategies need to be investigated in controlled settings and among different populations and distribution models in Nigeria.