BACKGROUND: Long-term cost-effectiveness analyses of health behaviour interventions to effectively manage type 2 diabetes mellitus (T2DM) in low-income countries are crucial for minimising economic burden and optimising resource allocation. Therefore, this study aimed to estimate the long-term cost-effectiveness of implementing a health behaviour intervention to manage T2DM in Nepal. METHODS: A Markov model in combination with a decision tree was developed to compare the costs and outcomes of the health behaviour intervention against usual care among 481 (238-intervention and 243-control) participants from healthcare system and societal perspectives. The model integrates empirical trial data, with published data to inform parameters not collected during the trial. The model estimated costs, quality-adjusted life years (QALYs) and cost-effectiveness over 5 years, 10 years, 20 years, 30 years and a lifetime time horizons with 3% annual discounting. Sub-group, scenarios, both one-way and two-way analyses and probabilistic sensitivity analyses (PSA) were performed to assess the impact of uncertainty in the model under the threshold of 3 times gross domestic product (GDP) per capita (i.e., US 140) for Nepal. RESULTS: Base-case analysis with lifetime horizon showed that the health behaviour intervention compared to usual care improved QALYs by 3.88 and increased costs by US 293 per patient, with an incremental cost-effectiveness ratio (ICER) of US 106 per QALY gained from a healthcare system perspective. From a societal perspective, QALYs also improved by 3.88 and costs increased by US 550, with an ICER of US 173 per QALY gained. Furthermore, the intervention demonstrated ICERs of US 36, US 78, US 37, and US 32 per QALY gained over 5-, 10-, 20-, and 30-year time horizons, respectively, from a healthcare system perspective, and US 19, US 66, US 59, and US 16 per QALY gained from a societal perspective. In the PSA, the probability of the health behaviour intervention being cost-effective was over 57%. CONCLUSIONS: The health behaviour intervention for managing T2DM was cost-effective over a lifetime horizon compared to usual care. To maximise its impact, this intervention should be scaled up nationwide, and future research is warranted to assess the long-term cost-effectiveness across diverse settings in low-income countries. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry (ACTRN12621000531819).