Depression is a common and serious psychological condition, which seriously affects individual well-being and functional ability. Traditional treatment methods include drug therapy and psychological counseling; however, these methods have different degrees of side effects and limitations. In recent years, nonconvulsive electrotherapy (NET) has attracted increasing attention as a noninvasive treatment method. However, the clinical efficacy and potential mechanism of NET on depression are still unclear. We hypothesized that NET has a positive clinical effect in the treatment of depression, and may have a regulatory effect on serum inflammatory factors during treatment. To assess the effects of NET on depression and analyze changes in serum inflammatory factors. This retrospective study enrolled 140 patients undergoing treatment for depression between May 2017 and June 2022, the observation group that received a combination of mindfulness-based stress reduction (MBSR) and NET treatment (n = 70) and the control group that only received MBSR therapy (n = 70). The clinical effectiveness of the treatment was evaluated by assessing various factors, including the Hamilton Depression Scale (HAMD)-17, self-rating idea of suicide scale (SSIOS), Pittsburgh Sleep Quality Index (PSQI), and levels of serum inflammatory factors before and after 8 wk of treatment. The quality of life scores between the two groups were compared. Comparisons were made using t and χ2 tests. After 8 wk of treatment, the observation group exhibited a 91.43% overall effectiveness rate which was higher than that of the control group which was 74.29% (64 vs 52, χ2 = 7.241; P < 0.05). The HAMD, SSIOS, and PSQI scores showed a significant decrease in both groups. Moreover, the observation group had lower scores than the control group (10.37 ± 2.04 vs 14.02 ± 2.16, t = 10.280; 1.67 ±0.28 vs 0.87 ± 0.12, t = 21.970; 5.29 ± 1.33 vs 7.94 ± 1.35, t = 11.700; P both < 0.001). Additionally, there was a notable decrease in the IL-2, IL-1β, and IL-6 in both groups after treatment. Furthermore, the observation group exhibited superior serum inflammatory factors compared to the control group (70.12 ± 10.32 vs 102.24 ± 20.21, t = 11.840; 19.35 ± 2.46 vs 22.27 ± 2.13, t = 7.508; 32.25 ± 4.6 vs 39.42 ± 4.23, t = 9.565; P both < 0.001). Moreover, the observation group exhibited significantly improved quality of life scores compared to the control group (Social function: 19.25 ± 2.76 vs 16.23 ± 2.34; Emotions: 18.54 ± 2.83 vs 12.28 ± 2.16; Environment: 18.49 ± 2.48 vs 16.56 ± 3.44; Physical health: 19.53 ± 2.39 vs 16.62 ± 3.46; P both < 0.001) after treatment. MBSR combined with NET effectively alleviates depression, lowers inflammation (IL-2, IL-1β, and IL-6), reduces suicidal thoughts, enhances sleep, and improves the quality of life of individuals with depression.