Low-dose naltrexone (LDN) has been suggested to target the multiple hallmarks of aging and improve healthspan metrics in humans. However, to date, no studies have evaluated LDNs potential as a gerotherapeutic. We collected real-world data utilizing the short form 36 quality of life (QoL) assay, immune status questionnaire, and a patient-reported health assessment to evaluate the effectiveness of LDN for improving multiple healthspan metrics in a normative aging cohort still within their healthspan. Most participants taking LDN for ≥3 months (69.2%) had a significant improvement in mean QoL scores (29.9%). The largest improvements were observed in the QoL categories of energy and fatigue, physical role limitations, emotional role limitations, social functioning, and pain. Participants also exhibited a significant improvement in mean immune function (24.6%). Data from a patient-reported health assessment at ≥4 weeks (N = 5500) and ≥10 weeks (N = 1450) of LDN use revealed that a majority of participants reported improvements in pain, fatigue, inflammation, and mood. A healthspan-enhancing drug should demonstrate the ability to enhance the health of individuals before significant age-related diseases and disability arise, thereby extending the period of life spent in good health. We found that 45% of responders to LDN had average to above-average baseline QoL scores, which increased to 76.6% of responders after LDN treatment. Furthermore, 23.8% of individuals taking LDN were able to discontinue other medications and 10.5% of participants reported avoiding planned clinical procedures. These data suggest that LDN might play a role in enhancing healthspan, warranting further research into its potential geroprotective effects.