Understanding physiological processes associated with mindfulness and compassion-based interventions is an emerging area of research interest. Of particular relevance is how such interventions can aid physiological health and well-being and by association stress and coping. In this regard, the study of alpha-amylase as a biomarker of autonomic nervous system activity and the stress response is increasing in popularity. In this chapter, we provide a brief overview of the biological basis of the stress response and how alpha-amylase is implicated, as well as review research where salivary alpha-amylase (sAA) has been utilized in the study of mindfulness and compassion. This literature provides good evidence to support the utility of sAA as an indicator of physiological well-being in mindfulness and compassion-based research. As such, we provide an overview of the reliability and validity of sAA in research protocols, before detailing collection and analysis methods. Given due diligence is needed in sAA research protocols, we additionally offer recommendations to aid the robustness of sAA methodology. To summarize, utilizing sAA in mindfulness and compassion-based research is recommended as a cost-effective and noninvasive physiological methodology that could support the efficacy of such interventions, as well as advance knowledge of associated underlying physiological processes.