Phytosterols (PSs) have been reported to improve blood lipids in patients with hypercholesterolemia for many years. However, meta-analyses of the effects of phytosterols on lipid profiles are limited and incomplete. A systematic search of randomized controlled trials (RCTs) published in PubMed, Embase, Cochrane Library, and Web of Science from inception to March 2022 was conducted according to the 2020 preferred reporting items of the guidelines for systematic reviews and meta-analysis (PRISMA) statement. These included studies of people with hypercholesterolemia, comparing foods or preparations containing PSs with controls. Mean differences with 95% confidence intervals were used to estimate continuous outcomes for individual studies. The results showed that in patients with hypercholesterolemia, taking a diet containing a certain dose of plant sterol significantly reduced total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (TC: Weight Mean Difference (WMD) [95% CI] = −0.37 [−0.41, −0.34], p < 0.001; LDL-C: WMD [95% CI] = −0.34 [−0.37, −0.30], p < 0.001). In contrast, PSs had no effect on high density lipoprotein cholesterol (HDL-C) or triglycerides (TGs) (HDL-C: WMD [95% CI] = 0.00 [−0.01, 0.02], p = 0.742; TG: WMD [95% CI] = −0.01 [−0.04, 0.01], p = 0.233). Also, a significant effect of supplemental dose on LDL-C levels was observed in a nonlinear dose–response analysis (p-nonlinearity = 0.024). Our findings suggest that dietary phytosterols can help reduce TC and LDL-C concentrations in hypercholesterolemia patients without affecting HDL-C and TG concentrations. And the effect may be affected by the food substrate, dose, esterification, intervention cycle and region. The dose of phytosterol is an important factor affecting the level of LDL-C.