Background: An increasing number of patients and practitioners are using mindfulness-based interventions despite inconsistency in the evidence supporting these programs' health benefits. Aim: To review the current evidence on the effectiveness of mindfulness-based interventions on depressive symptoms and quality of life among patients with depression comorbid medical conditions and those with major depressive disorder. Methods: A comprehensive search of PubMed, Ovid MEDLINE, and PsycINFO was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for English-language articles published over the past 30 years (1987-2017). The following keywords were used: meditation, QOL, depression, and mindfulness. Based on the consensus of two reviewers, 16 studies were selected for inclusion in this study. Results: We included randomized controlled trials that utilized mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy (MBCT), and other interventions based on MBSR and MBCT protocols. Overall, these interventions showed significant improvement in depressive symptoms (Cohen's d= 0.04-1.06) and quality of life (Cohen's d= 0.05-1.09) at post-treatment (8 weeks) compared to usual care, waitlist-control, active control (psychoeducation, exercise, and muscle relaxation), and evidence-based treatment (antidepressants). The interventions were found to be useful, especially among patients with depression dealing with chronic pain, cancer, multiple sclerosis, amyotrophic lateral sclerosis, irritable bowel syndrome, and insomnia. Conclusions: MBSR, MBCT, and mindfulness interventions that modeled MBSR/MBCT demonstrated efficacy as a treatment for depressive symptoms (alone or with adjunctive therapy) among patients suffering from depression comorbid medical conditions and those with major depressive disorder.