Infectious diseases pose a substantial threat to global health security. Key wildlife species, potentially harbouring numerous zoonotic pathogens, are increasingly being forced to adapt to disturbances from land-use change, human encroachment and climate change. Although the evidence is rather convincing pertaining to the increased risks of zoonotic diseases with degradation and disturbances, the scientific literature on the mitigating effects of ecosystem restoration on zoonotic spillover is scattered, inconclusive and challenged by the lack of a conceptual framework and practical guidance. In light of rising restoration needs and activities, we outline six critical considerations when examining impacts of zoonotic diseases from ecosystem restoration: (1) assessment of zoonotic disease targets; (2) time lag between restoration and recovery; (3) integration of trophic rewilding; (4) robust study designs; (5) controlling for confounding and modifying drivers; and (6) stakeholder engagement and co-creation with communities. Failure to account for these considerations makes the scientific contribution of restoration less valuable and may even jeopardize global efforts to reverse the global biodiversity decline.