Lesbian, gay, bisexual, transgender, and queer (LGBTQ), female sex workers (FSW), and heterogenders are those unconventional groups of the society who are identified with major unacceptance. Thus, the present study is conducted to assess and compare the oral health status, substance abuse pattern and nicotine dependence using Fagerstrom nicotine dependence scale (FNDP) among the LGBTQ, FSW, and heterogender in a defined location of Gautam Buddha Nagar, district in West U.P. The present exploratory research included three study groups, the LGBTQ, FSW, and heterogenders (HG) residing in the same habitat. Purposive snowball sampling was conducted for the accessibility of the unapproachable population in the defined geographical location at Gautam Budha Nagar, district in West Uttar Pradesh. The data collection of a total of 177 participants was done using a pre-validated, pretested proforma consisting of three different parts including WHO oral health assessment form for adults, 2013, questionnaire regarding pattern of substance abuse and FNDS. Data were recorded and statistically analyzed using SPSS. Prevalence of oral health disorders including dental caries, periodontal disease as well as oral mucosal lesions were more commonly found among the LGBTQ participants followed by FSW and the differences were found to be statistically significant. In context of altered habits, 100% of the participants in the present study were reported with smokeless tobacco habits whereas majority of the FSW were reported with a habit of smoking tobacco. In addition to belonging to ethnic and sexual minority, and having minimal or low education status, and low socioeconomic status, the present study groups are reported to have suboptimal access to quality healthcare and are further reported with high level of substance abuse as well as nicotine dependence. The present study is an attempt to provide base line data for further research and provide data to the policy makers so as to increase the healthcare access to the present groups. How to cite this article: Sharma S, Shukla S, Kamate SK, et al. An Exploratory Research Comparing Oral Health, Pattern of Substance Abuse and Nicotine Dependence among LGBT, Female Sex Workers and Heterogenders. J Contemp Dent Pract 2023;24(12):991-997.