Background: End-stage renal disease (ESRD) necessitates hemodialysis (HD), a treatment associated with substantial physical and psychological burdens. Anxiety and depression are common in ESRD patients and can adversely impact their quality of life and treatment adherence. This study aimed to evaluate the prevalence of anxiety and depression among patients undergoing chronic HD. Methods: A cross-sectional observational study was conducted at SRMS IMS Bareilly involving 100 ESRD patients on chronic HD. Patients completed the Hospital Anxiety and Depression Scale (HADS) to evaluate symptoms of anxiety and depression. Results: Among the 100 patients, 68% exhibited depressive disorders, and 56% had anxiety disorders, with 24% showing both conditions. Depression was more prevalent among males (62.86%) compared to females (44.7%)-ODDs ratio-1.29. In contrast, anxiety was significantly higher in females (44.3%) compared to males (31.8%)-ODDs ratio-0.69. The prevalence of depression and anxiety varied across age Depression increases with age, being highest in individuals aged ≥60 years and lowest in those aged 18–39 years. Patients undergoing HD three times a week reported more depressive symptoms. Additionally, the use of central venous catheters correlated with increased psychological symptoms. Conclusions: Depression and anxiety are prevalent among ESRD patients on HD, with significant gender disparities and an association with HD frequency. Addressing these psychological aspects through comprehensive care strategies is essential for improving patient outcomes.