Background <p>Mental disorders are widely recognised as a major contributor to morbidity in prisons across the European Union, with evidence consistently indicating a markedly higher mental health burden among incarcerated individuals compared with community populations. Prison research has mainly focused on mental illness, often neglecting protective aspects of mental health from a salutogenic perspective. In Portugal, previous studies have examined specific mental health outcomes in prison populations, such as suicidal behaviour, personality pathology, trauma-related symptoms, or substance use; however, integrative research simultaneously encompassing multiple mental health symptoms, positive psychological constructs, and associated psychosocial factors remains limited. This study seeks to address this gap by evaluating mental health symptoms (stress, anxiety and depression), substance use, and positive psychological constructs (resilience, hope and psychological well-being) among adult incarcerated individuals and to explore factors associated with resilience as a secondary, hypothesis-generating analysis.</p> Methods <p>A cross-sectional study was conducted with 576 incarcerated individuals in mainland Portugal. Data were collected using the 10-item Connor–Davidson Resilience Scale (CD-RISC-10), the 21-item Depression, Anxiety and Stress Scale (DASS-21), the Herth Hope Index (HHI), the Psychological Well-Being Manifestation Scale (PWBM-S), five items from the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), and a sociodemographic and legal-criminal questionnaire. Multiple mental health domains were characterised and explored factors associated with resilience as a secondary hypothesis-generating analysis. Multivariable linear regression was used to examine associations between resilience and candidate sociodemographic, clinical, and psychosocial factors.</p> Results <p>The DASS-21 indicated mean scores of 4.7 for anxiety, 4.9 for depression, and 6.2 for stress. Mean scores on the CD-RISC-10 29.1, HHI 31.2, and PWBM-S 96.9 are reported. The greatest risks of substance dependence were observed for tobacco, alcohol, cannabinoids and cocaine. Multiple linear regression suggested psychological support prior to incarceration, an open prison regime, the ability to cope with negative emotions, engagement in physical activity, face-to-face contact with family and friends, practice of relaxation techniques and regular reflection on the reasons for incarceration were positively associated with higher resilience levels. By contrast, exposure to verbal and/or physical aggression was inversely associated with resilience levels.</p> Conclusions <p>These findings highlight the urgent need to design and implement structured, multidimensional, and evidence-based interventions to strengthen resilience and improve mental health among people in prison.</p> Clinical trial number <p>Not applicable.</p>