Substance use disorder is a global mental health issue. Purpose in life, Loneliness and depression are key indicators of poor mental health, and people with substance use disorder are more likely to experience low purpose in life, depression, and loneliness. This study aims to further the understanding of purpose in life, depression and loneliness among substance use disorders (SUD) patients in three hospitals in Ghana. It uses a cross-sectional survey design. A total of 425 SUD inpatients were screened. Beck Depression Inventory-II, the revised UCLA Loneliness Scale, and the Purpose in Life Test were utilised to measure depression, loneliness, and purpose in life respectively. Data were analysed using the SPSS version 23 for Windows. Data from 378 participants were collected for this study using a cross sectional survey design; after data cleaning, frequency tables (for categorical variables) and descriptive statistics (for continuous variables) were used to summarise the demographics and the three outcome variables depression, purpose in life, and loneliness. Our findings indicate that overall, participants are more likely to experience low sense of purpose in life, depression, and loneliness compared to the general population. There was no statistically significant relationship between depression and loneliness (r = 0.030, p = 0.567). There was a statistically significant negative relationship between depression and purpose in life (r = -0.514, p < 0.001). There was a statistically significant positive relationship between purpose in life and loneliness (r = 0.147, p = 0.004). There was no gender difference in depression, purpose in life, and loneliness among SUDs patients in psychiatric hospitals. There were no significant differences in purpose in life, depression and loneliness based on marital status. It is anticipated that the findings of this study will inform policies and clinical practice regarding service provision for patients with SUDs.