Background <p>Sleep disruption and circadian dysregulation are common in patients admitted to the intensive care unit (ICU) and are associated with adverse recovery outcomes. Non-pharmacological nursing strategies such as environmental control and clustered care are widely implemented to reduce nocturnal disturbance, yet their physiological effects remain uncertain. Melatonin may serve as a potential marker of circadian processes; however, its interpretation depends on temporal dynamics that are not consistently captured across studies.</p> Methods <p>This systematic review and meta-analysis of randomized controlled trials evaluated the effects of non-pharmacological ICU nursing interventions on melatonin concentrations, with secondary analyses of cortisol levels and sleep quality. PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were searched from inception to February 7, 2026. Random-effects meta-analysis using Hedges’ g was performed. Risk of bias was assessed using the Cochrane RoB 2.0 tool and certainty of evidence using GRADE. The review was prospectively registered in PROSPERO (CRD420261303901) in February 2026.</p> Results <p>Five randomized trials were included. Non-pharmacological nursing interventions were associated with higher measured melatonin concentrations compared with usual care (Hedges’ g = 0.28, 95% CI 0.08–0.49, <i>p</i> = 0.01; I² = 5.4%). However, in the absence of temporal profiling, this finding cannot be interpreted as evidence of circadian alignment. Cortisol outcomes showed no significant difference (Hedges’ g = − 0.11, 95% CI − 0.83–0.61, <i>p</i> = 0.76; I² = 86.8%). Sleep quality outcomes were inconclusive, with substantial heterogeneity across studies (Hedges’ g = 1.22, 95% CI − 0.05–2.48, <i>p</i> = 0.06; I² = 94.3%). Certainty of evidence was low for melatonin and very low for other outcomes due to risk of bias, imprecision, and inconsistency.</p> Conclusions <p>Non-pharmacological ICU nursing care was associated with modest increases in melatonin concentrations; however, the clinical significance of this finding remains uncertain, and no consistent benefits were observed for perceived sleep quality or cortisol concentrations. These findings suggest that such interventions may be associated with higher nocturnal melatonin concentrations, although their effects on patient-centered clinical outcomes remain unclear. Further large, well-designed trials are required to confirm these findings.</p> PROSPERO registration number <p>Registered in PROSPERO (CRD420261303901).</p>