Zinc supplementation is a critical adjunct therapy for managing acute childhood diarrhoea, particularly in low-income countries (LICs) and lower middle-income countries (LMICs). However, adherence to the recommended zinc regimen remains a major challenge, limiting its effectiveness in real-world settings. This systematic review and meta-analysis aimed to estimate the pooled adherence rates to zinc supplementation for diarrhoea in children under 5 and identify key determinants of adherence. A comprehensive search of PubMed, Embase, Scopus, Google Scholar, ProQuest, and CINAHL was conducted between 2000 and 2024. A total of 10 observational studies were included, with pooled adherence of 63.45% (95% CI: 51.62–75.28) for 10 days regimen and 34.58% (95% CI: 7.08–62.09) for 14 days regimen, along with high heterogeneity. Sensitivity analysis confirmed robustness of these estimates. Key factors associated with adherence included caregiver education, provider counselling, medication acceptability, and economic constraints related to caregiver buying capacity. Doi plot asymmetry suggested possible publication bias for 10 and 14 days regimen. Overall, adherence to zinc therapy remains sub-optimal, particularly for 14 days regimen compared to 10 days regimen. Targeted interventions addressing behavioural, provider, and formulation related barriers are urgently needed to optimize zinc adherence and improve diarrhoea outcomes globally.