Summary Clinical trials have investigated the weight loss effect of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) in adults with obesity without diabetes mellitus, but results for weight loss efficacy were varied. We aimed to provide an up‐to‐date systematic review and meta‐analysis for overall weight loss effect of GLP‐1 RA in adults with obesity and overweight without diabetes mellitus. We retrieved eligible randomized control trials that assessed the weight loss effect of GLP‐1 RA in adults (≥18 years old) without type 1/type 2 diabetes up to September 30, 2021, using Pubmed and Embase. Of 36 clinical trials assessed for eligibility, 12 trials were included, with a combined total of 11,459 participants. Compared with control groups, a more significant weight loss was seen in GLP‐1 RA groups with an overall mean difference of −7.1 kg (95% CI −9.2 to −5.0) (I2 = 99%). The overall analysis results showed that GLP‐1 RA improved glycemic control without increasing the risk of hypoglycemic events. Better control of blood pressure and plasma levels of LDL, HDL, and triglycerides was seen with GLP‐1 RA treatment. Subgroup analysis showed greater treatment effect of semaglutide than liraglutide. Vomiting, nausea, dyspepsia, diarrhea, constipation, and abdominal pain were GLP‐1 RA‐associated common adverse effects.