Substance abuse constitutes a global problem and one of the most important risks taking behaviour among secondary schools students in Nigeria. Adolescents are more susceptible to substance abuse due to peer pressure. The study therefore, evaluates the adolescents’ knowledge, perceived susceptibility of peer relationships on substance abuse in selected secondary schools in Ikenne Government Area in Ogun State. Descriptive survey design was adopted for the study. Random sampling technique was used to select 300 respondents. The Adolescent Knowledge and Susceptibility Scale (AKAS) questionnaire was used to obtain information from the respondents. Descriptive statistics, Pearson Product Moment Correlation, T-test and ANOVA were used to analyze the data collected to provide answers to the four hypotheses raised for the study. Findings indicate that 91.7% of the respondents are knowledgeable about substance abuse. A significant relationship exists in adolescents’ knowledge and perceived susceptibility to substance abuse (cal t = 0.493, sig. @ crit t = 0.163, P < .05). Similarly, significant difference exists in the male and female adolescents’ perceived susceptibility to substance abuse (Crit-t =1.96, Cal, t = 2.267, Df = 297, P < .0). Also, family type was significant in influencing adolescents’ knowledge of substance use and perceived susceptibility to substance abuse. (Crit-t = 0.289, Cal. F = 2.769, df = 298, P < .05). The study recommends that Government should tackle the problem of substance use through campaigns, seminars and rallies; psychosocial screening, providing orientation programme for parents, media campaigns, involving professional medical practitioners and counseling psychologists and regular house to house anti-drug abuse campaign by local community town criers. Also, there is the need for every school to have counseling centers. Parents should not only educate their adolescent children on the adverse effect of substance abuse on health but also monitor the type of friends their children keep.