Drug addiction is a complex disorder caused by multiple factors, including environmental and genetic factors. Stress-related genes such as Galanin (GAL) and Oxytocin (OXT) have been linked to the reward pathways that contribute to the development and progression of substance addiction. This study aimed to explore the correlation between several polymorphisms of stress-related genes and drug addiction among Jordanian males. The study included 500 participants, consisting of both healthy controls and drug-addicted Jordanian males. The genetic material and clinical data were collected, and 18 SNPs in four candidate genes were genotyped using the Sequenom MassARRAY® system. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 25.0 and the SNPStats website. The study identified a significant correlation between three SNPs of the GAL gene and drug addiction, specifically rs3136544, rs3136541, and rs694066. The study also found that different genotypes of these variants were significantly associated with drug addiction. Furthermore, different haplotypes of the GAL, GALR1, and OXTR polymorphisms were also significantly correlated with drug addiction. The study also identified a correlation between several drug addiction features and the studied variants, including the association of rs2717162 of Galanin receptor 1 (GALR1) with age at use onset and the association of rs3136541 of GAL with the type of substance and number of substances used. Stress-related genes can play a significant role in the development and progression of addiction among the Jordanian population, and further investigations are necessary to understand the underlying mechanisms better and improve future treatment strategies.