Gabapentinoids (e.g., gabapentin and pregabalin) have been established as a treatment for postherpetic neuralgia (PHN), but their effects on the prevention of PHN are unclear. This systematic review aimed to evaluate the efficacy of gabapentinoids for acute herpes zoster (HZ) in preventing PHN. PubMed, EMBASE, CENTRAL, and Web of Science were queried December 2020 to collect data on relevant randomized controlled trials (RCTs). A total of four RCTs (including 265 subjects) were retrieved. Overall, the incidence of PHN was lower, but not statistically significant in the gabapentinoid-treated group compared to the control group. Subjects treated with gabapentinoids were more likely to experience adverse events such as dizziness, somnolence, and gastrointestinal symptoms. This systematic review of RCTs showed that the addition of gabapentinoids during acute HZ are not significantly effective in preventing PHN. Nevertheless, the evidence on this subject remains limited. Physicians should carefully weigh the risks and benefits of prescribing gabapentinoids during the acute phase of HZ owing to its side effects.