This systematic review investigated the psychological and physiological effects of the human-animal bond (HAB) and animal-assisted interventions (AAI) on mental health and stress reduction. Published studies from 2000 to 2023 were analyzed. The review explored the theoretical underpinnings of AAI, the role of HAB in AAT, and the psychosocial and psychophysiological outcomes of human-animal interaction (HAI). Findings suggest HAI can reduce anxiety, depression, and loneliness, and influence blood pressure, heart rate, and hormones associated with well-being (oxytocin, b-endorphin, prolactin, phenylacetic acid, dopamine). Oxytocin activation appears to play a key role in these effects. AAI, including AAT, can buffer stress and provide emotional and social support, enhancing resilience.