Mindfulness-based interventions (MBIs) have been consolidated in healthcare settings as a highly useful therapeutic approach. Numerous studies have demonstrated their positive influence on physical and psychological well-being. In contrast, the scientific evidence concerning the potential beneficial effects of mindfulness on biological variables such as health indicators is still scarce. Therefore, in this study, we sought to analyse the influence of a mindfulness and self-compassion-based intervention on levels of salivary immunoglobulin A (sIgA) in order to validate its use in field studies. A secondary objective of the study was to confirm the associated decline in salivary cortisol (Csal) levels and improvements in self-reported health and mood already described in the general population. For this purpose, we conducted a longitudinal design, collecting saliva samples and self-reports before and immediately after the first and the last session of the intervention. Results show an improvement in health and self-reported mood, along with an increase in the sIgA levels of participants and a reduction in Csal levels. These results reinforce existing evidence of the beneficial effects of mindfulness and self-compassion on health, evaluated from a holistic perspective, considering both biological and self-reported variables. Moreover, as already done with other biological indicators such as Csal, sIgA could be used in clinical settings to evaluate the effectiveness of MBIs.