The Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI) South Africans continue to face considerable challenges, including societal stigma, homophobic violence (particularly corrective rape), and high rates of sexually transmitted diseases and infections (particularly Human Immunodeficiency Virus (HIV)/AIDS) even when discrimination based on sexual orientation was outlawed by South African’s post-apartheid constitution. This study was conducted to ascertain violence, abuse and discrimination against the LGBTI sector as key factors that hinder the smooth implementation of HIV/AIDS programme among sexually minority (LGBTI) group in Walter Sisulu University, South Africa. The self-structured questionnaire was used to collect data. The study involved 3048 purposively selected participants (1285 male and 1763 female) aged 17–38 years. About 70.5% of the participants witnessed physical attack as a form of violence against people in same-gender relationship; 47.7% disagreed that violent targeted at this sexually minority group is justified. The LGBTI face challenges which include verbal insults (937, 32.4%), bullying (532, 18.4%) and name-calling (1389, 48%). Discrimination against members of the LGBTI sector was witnessed in various forms: non-acceptance (981, 33.9%), disapproval of act of homosexuals (1308, 45.2) and denial of rights (327, 11.3). Violence, abuse and discrimination which constitute stigmatisation among the LGBTI sector are received with mix feeling. Some respondents justified the use of one or more of these key elements of stigmatisation against the LGBTI (6.6%, supports violence), others condemned these acts of stigmatisation (28.8%), against discrimination). Social stigma which resulted from violence, abuse and discrimination exist in this institution and is responsible for the unwillingness of disclosure of sexual orientation among the LGBTI members. An enabling environment should be created where the LGBTI members could come out freely to access programmes targeted at the prevention and control of HIV/AIDS.