Mild cognitive impairment (MCI) is the prodromal stage of dementia. In this stage, reasonable intervention measures can help to delay the decline of cognitive function. Supplementation of n-3 polyunsaturated fatty acids (n-3PUFAs) may be beneficial to delay the decline of cognitive function in the elderly. To investigate the effectiveness of docosapentaenoic acid (DHA) or/and eicosapentaenoic acid (EPA) supplements in the elderly with MCI. Eight electronic databases, PubMed, Cochrane Library, Embase, VIP, SinoMed, Web of Science, CNKI, and WANFANG DATA, were searched for related articles from inception until January 2022. Subgroup analyses and sensitivity analyses were performed to detect confounding variables. Standardized mean differences (SMD) with 95% confidence intervals (CI) were determined. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots. Stata12.0 was used for Begg's and Egger's test to quantify whether publication bias. Linear relationship between global cognition and covariates was examined in meta-regression analysis. Twelve studies (n = 1,124) were included. The methodological quality of research is mostly medium. Compared with placebo, n-3PUFAs supplements have benefits on global cognition [SMD = 0.51, 95% CI(0.12, 0.91), p = 0.01]. No significant differences were observed between intervention group and placebo on language fluency, executive functions, and depression. Our findings indicated DHA and/or EPA supplements have benefits on global cognition, and it may also reduce the level of blood amyloid-β (Aβ)-related biomarkers (e.g., Aβ40, Aβ42) and inflammatory factors (e.g., 1L-6, 1L-10). Since there are only two relative articles, more research is needed in the future to clarify the relationship.