Abundant research has shown that Christian religiosity inhibits adolescent substance use, especially in communities where most of the population shares the same religious values and beliefs. Due to the lack of empirical research, it is unclear if Christian religiosity has the same inhibitory influence in predominantly secular and religiously diverse societies. This study aims to bridge this gap and thereby improve our understanding of the relationship between Christian religiosity and delinquent behavior in different cultural contexts. Through the analysis of survey data collected from a large probability sample of adolescents in China's special administrative region of Macau, this study found a strong inverse relationship between Christian religiosity and adolescent substance use, despite the predominantly secular nature of Macau society. In contrast, religious commitment among non-Christian youths showed no relationship with substance use. The theoretical and practical implications of the findings are discussed.