The field of nanozymes is developing rapidly. In particular, glutathione peroxidase (GPx)-like nanozymes, which catalytically reduce H2O2/organic hydroperoxides to H2O/alcohols, have attracted considerable attention. GPx-like nanozymes are powerful antioxidant enzymes known to combat oxidative stress. They have broad applications, including cytoprotection, anti-inflammation, neuroprotection, tumor therapy, and anti-aging. Although much progress has been made, GPx-like nanozymes have not been well discussed or fully reviewed as other nanozymes. This review aims to summarize recent advances on GPx-like nanozymes from the vantage point of mechanism, classification, and bioapplication. Future prospects for advancing their design and application are also discussed.