Depression and anxiety remain major mental health challenges worldwide and are on the rise in India. While many individuals benefit from medication, a significant number report only partial relief or discontinue treatment due to adverse effects. This has led to the development of integrative models of care. One such approach is the Psycho-Nutritional Intervention Approach (PNIA), which combines diet, yoga, mindfulness, and counselling. Ayurveda adds another dimension by emphasizing daily routines, rejuvenating herbs, and healing therapies such as Shirodhara. Our trial evaluated whether PNIA would demonstrate enhanced efficacy when augmented with Ayurvedic interventions. We conducted a randomized study involving 120 participants aged 18–55 years who reported mild to moderate symptoms of anxiety and depression. All participants followed PNIA. Those in the integrative arm additionally received standardized Ashwagandha and Brahmi tablets, a seven-day course of Shirodhara, and lifestyle counselling. The program lasted twelve weeks. Outcomes were assessed using international scales, Indian instruments measuring disability and self-efficacy, and specific biological markers. Results revealed a clear trend: the PNIA-plus-Ayurveda group reported greater improvements in depression and anxiety symptoms, along with enhanced quality of life and daily functioning. Biological markers supported these findings, showing reduced stress levels and increased neurotrophic support. Importantly, both programs were safe and well received. These findings suggest that PNIA’s efficacy is enhanced when supplemented with Ayurvedic treatments. This combined model represents a culturally sensitive and potentially scalable approach to community-based mental health care.