The advantage of endoscopic submucosal dissection (ESD) is that it is less invasive than surgery. ESD is one of the best treatments for older patients as surgery in this age group of patients is difficult. However, it is unclear how much lower the physical stress of ESD is compared with that of surgery. Thus, objective methods are required to assess physical stress in patients who have undergone ESD. The current review of ESD aimed to summarize the recent advancements in the assessment of physical stress during the perioperative period, focusing on changes in energy metabolism and serum opsonic activity (SOA). Based on metabolic changes, resting energy expenditure (REE) was measured using an indirect calorimeter. The stress factor calculated from the REE and the basal energy expenditure computed using the Harris-Benedict equation can be used to assess physical stress. SOA was assessed using the chemiluminescence method, wherein the use of chemiluminescent probes (i.e., lucigenin and luminol) allowed quantification of reactive oxygen species generated by neutrophils. Using an auto luminescence analyzer, the results were evaluated based on the maximum light emission and area under the emission curve. These quantifiable results revealed the minimal invasiveness of ESD.