Background <p>Type 2 diabetes has been associated with impaired thermoregulatory responses to increased core body temperature, making patients more vulnerable to heat-related disorders. Although recent studies have investigated these diabetes-related impairments in heat loss mechanisms, our understanding of the occurring phenomena remains unclear due to the complexity of results and the various factors contributing to increased core body temperature.</p> Objective <p>To address the following Population/Exposure/Comparator/Outcome (PECO) question: what is the effect of an increase in core body temperature level (E) on the vasomotor and sudomotor responses and the physiological and molecular mechanisms that control these responses (O) within individuals with type 2 diabetes (P) compared to healthy individuals at the same level of core body temperature (between-group comparisons) and/or type 2 diabetes patients at lower or normal core body temperature level (within-group comparisons) (C)?</p> Methods <p>This protocol will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A thorough database search will be conducted in PubMed and Embase using tested and validated search algorithms. Experimental (randomized and non-randomized controlled trial) or observational studies with type 2 diabetes populations and have measured core body temperature will be included. A narrative synthesis will be conducted and if possible, meta-analysis will be performed. Risk of bias will be assessed using the Office of Health Assessment and Translation tool.</p> Discussion <p>The results from this review will expand our knowledge of the physiological mechanisms through which type 2 diabetes impairs heat loss under hyperthermic conditions and inform guidelines to mitigate heat-related risks in type 2 diabetes populations.</p> Systematic review registration <p>PROSPERO CRD42023471939.</p>