BackgroundCaffeine is often used as a stimulant during fatigue, but the standard of characteristic physiological indicators of the effect of caffeine on neuromuscular fatigue has not been unified. The purpose of this systematic review and meta‐analysis is to summarize current experimental findings on the effects of caffeine on physiological indexes before and after neuromuscular fatigue, identify some characteristic neuromuscular physiological indexes to assess the potential effects of caffeine.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta‐analyses are followed. We systematically searched PubMed, Google academic, and Web of Science for randomized controlled trials. We searched for studies on caffeine's (i) effects on neuromuscular fatigue and (ii) the influence of physiological indexes changes. Meta‐analysis was performed for standardized mean differences (SMD) between caffeine and placebo trials in individual studies.ResultsThe meta‐analysis indicated that caffeine significantly improves voluntary activation (VA) (SMD = 1.46;95%CI:0.13, 2.79; p < .00001), PTw (SMD = 1.11, 95%CI: –1.61, 3.84; p < .00001), and M‐wave (SMD = 1.10, 95%CI: –0.21, 2.41; p < .00001), and a significant difference (p = .003) on measures of Peak Power (PP), and insignificant difference on measures of heart rate (HR) (I 2 = 0.0, p = .84) and Maximal oxygen uptake (VO2) (I 2 = 0.0, p = .76).ConclusionThe analysis showed that caffeine intake had a relatively large effect on VA, potentiated twitch (PTw), M‐wave, which can be used as characteristic indexes of caffeine's impact on neuromuscular fatigue. This conclusion tends to indicate the effects of caffeine on neuromuscular fatigue during endurance running or jumping or muscle bending and stretching. The caffeine intake had a big effect on the electromyogram (EMG) and peak power (PP), and its effect role needs to be further verified, this conclusion tends to indicate the effect of caffeine on neuromuscular fatigue during jumping or elbow bending moment movements. HR, VO2, maximal voluntary contraction (MVC) cannot be used as the characteristic indexes of caffeine on neuromuscular fatigue. This conclusion tends to indicate the effect of caffeine on neuromuscular fatigue during endurance exercise. However, the results of meta‐analysis are based on limited evidence and research scale, as well as individual differences of participants and different physical tasks, so it is necessary to interpret the results of meta‐analysis cautiously. Therefore, future research needs to explore other physiological indicators and their indicative effects in order to determine effective and accurate characteristic indicators of caffeine on neuromuscular fatigue.