Background: Psychoactive substance use among adolescents continues to be a public health challenge, considering the physical and mental health consequences of this risk behavior. Most studies done in Nigeria on psychoactive substance use among adolescents are prevalence studies (quantitative) but there remains the great need for studies on probable association with some factors such as those relating to the family. Aims/Objectives: This current study endeavored to ascertain the relationship between risk and protective family factors (qualitative) and psychoactive substance use among adolescents in secondary schools in Ido–Ekiti and its environs. Additionally, prevalence of psychoactive substance use was also determined. Method: The study was a cross–sectional descriptive study among randomly selected students of secondary schools in classes (JSS3, SS1 & SS2) in Ido–Ekiti area. The sample was truly adolescents’ (mean age =14.5±1.4years). The following instruments were combined into one composite questionnaire: World Health Organization (WHO) students’ drug use questionnaire, Family APGAR scale (APGAR is an acronym which stands for Adaptability, Partnership, Growth, Affection, and Resolve), General Health Questionnaire (GHQ–12) and Parenting Styles Questionnaire (PSQ). The questionnaire was used to obtain information on family factors and psychoactive substances use from the respondents. Anonymity and confidentiality were assured to minimize inaccuracy of responses due to fear of reprisal with drug use. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 16.0 for Window. Results: A total of 348 adolescents were studied. Forty six percent (n=161) were males while 54% (n=187) were females. With regards to gender, the lifetime prevalence rate for at least one psychoactive substance use was higher for males 46% (n=74) than that of the females 28.9% (n= 54). The mean age was 14.5 years. 57.2% (n=199) lived with both parents, 18.7% (n=65) lived with their mother and 5.7% (n=20) lived with their father. The commonest substances used by the respondents were Alcohol (21.6%), Analgesics (8.6%), Tobacco (8.3%), Sedatives (7.8%), and Cannabis (7.5%). The prevalence rates for lifetime use varied from 4.0% (n=14) for Heroin and 21.6% (n=75) for Alcohol. Grossly, the lifetime prevalence rate for at least one psychoactive substance use was 36.8% with 95% CI (31.9–42.0). By and large, Alcohol use by father (OR = 4.463, 95% CI 1.621–12.285), Tobacco use by sibling (OR = 14.023, 95% CI 1.628–117.165), moderately dysfunctional family (OR = 2.344, 95% CI 1.223–4.492) and Age groups: 12–13 years & 14–15 years with (OR 0.0151, 95% CI 0.064–0.355) and (OR= 0.263, 95% CI 0.132–0.525) respectively were identified as factors for the use of Psychoactive substances among adolescents in this study. Conclusion: The prevalence of psychoactive substance use among secondary schools adolescents studied was disturbingly high and this could be attributed in part to family members’ drug use behavior, family dysfunctions and mid adolescence age group. While drug use behavior by family members and family dysfunctions were risk factors, the younger age group was protective. There is the need to put preventive measures in place at various level of child training against substances use in secondary schools. Further studies would be needed in this area