Food habits and oral hygiene are critical attributes for physiochemical environment of the oral cavity. Consumption of intoxicating substances such as betel nut (’Tamul’), alcohol, smoking and chewing tobacco may strongly influence the oral ecosystem including commensal microbes. Therefore, a comparative assessment of microbes in the oral cavity between individuals consuming intoxicating substances and non-consumers may indicate the influence of these substances. Oral swabs were collected from consumers of intoxicating substances and non- consumers of Assam, India, microbes were isolated by culturing on Nutrient agar and identified by phylogenetic analysis of their 16S rRNA gene sequences. The risks of consumption of intoxicating substance on occurrence of microbes and health conditions were estimated using binary logistic regression. Mostly pathogens and opportunistic pathogens were found in the oral cavity of consumers and oral cancer patients which includedPseudomonas aeruginosa,Serratia marcescens,Rhodococcus antrifimi,Paenibacillus dendritiformis,Bacillus cereus,Staphylococcus carnosus,Klebsiella michiganensisandPseudomonas cedrina.Enterobacter hormaecheiwas found in the oral cavity of cancer patients but not in other cases.Pseudomonas sp. were found to be widely distributed. The risk of occurrence of these organisms were found in between 0.01 and 2.963 odds and health conditions between 0.088 and 10.148 odds on exposure to different intoxicating substances. When exposed to microbes, the risk of varying health conditions ranged between 0.108 and 2.306 odds. Chewing tobacco showed a higher risk for oral cancer (10.148 odds). Prolonged exposure to intoxicating substances conduce a favorable environment for the pathogens and opportunistic pathogens to colonize in the oral cavity of individuals consuming intoxicating substances.