Background: Severe mental illnesses (SMIs), including schizophrenia and bipolar disorder affect patients significantly. Gender has been identified as a key factor influencing the experience of SMIs with notable disparities in prevalence, symptoms, and treatment outcomes. Additionally, the quality of life (QoL) and social support for patients with SMIs can vary based on gender. Aims: This study examined gender differences in QoL and social support of patients with SMIs. Method: Participants include 170 outpatients with schizophrenia and bipolar disorder at Shafa Hospital (2021). QoL and social support were assessed using World Health Organization QoL (WHOQOL-BREF) questionnaire and Medical Outcomes Study Social Support Survey (MOS-SSS), respectively. Group differences were analyzed using t-test or Mann–Whitney U test, and two-way multivariate analyses of variance explored the effect of gender and disease type. Results: It was indicated that females with schizophrenia reported higher QoL than males, but the opposite was observed for bipolar disorder. Gender differences in social support were not significant among schizophrenia patients, nor between the two patient groups. However, women with bipolar disorder and multiple hospitalizations experienced lower social support and QoL compared to men. Additionally, more hospitalizations were associated with decreased QoL in both genders with schizophrenia. Conclusions: Findings suggest the need for gender- specific interventions and support policies to enhance QoL and social support in patients with SMI.