Objective: The purpose of this systematic review is to synthesise the available evidence of the impact of therapy dog-assisted interventions on the social and emotional wellbeing of students in mainstream school settings through the use of the biopsychosocial framework. Method: The PRISMA 2020 guidelines were followed, and the inclusion criteria included primary outcomes related to social and emotional wellbeing, such as social competencies and mental health. The studies included were conducted in mainstream educational settings, incorporated a therapy dog, provided a comparison or control group and were in English. The quality of the evidence was assessed with the Evidence Project Risk of Bias tool. Results: Of 405 studies identified, seven studies with sufficient rigour met the inclusion criteria of evidence to support the use of therapy dog-assisted interventions to improve social and emotional wellbeing within a school setting. Outcomes consisted of psychological, biological, and social variables contributing to overall wellbeing, such as improved self-perceptions, decreased cortisol levels and improvement in social behaviour and empathy. Conclusions: Findings suggest that therapy dog-assisted interventions can have a positive impact on social behaviours and reducing stress in a school setting; however, there is a need for more rigorous and current research investigating therapy dog-assisted social and emotional wellbeing interventions in mainstream educational settings.