Objective To investigate the effect of anesthesia depth on intraoperative calcitonin gene‑related peptide (CGRP) and substance P (SP) in diabetic patients. Methods A total of 78 patients, aged 42‒70 years old, American Society of Anesthesiologists (ASA) grades Ⅰ or Ⅱ, who were scheduled for laparoscopic surgery under general anesthesia were enrolled. According to the presence of type 2 diabetic mellitus, they were divided into two groups: a non‑diabetic (NDM) group (n=40) and a diabetic (DM) group (n=38). According to the random number table method, they were then divided into four groups: a light anesthesia non‑diabetic (LNDM) group (n=20), a deep anesthesia non‑diabetic (DNDM) group (n=20), a light anesthesia diabetes (LDM) group (n=19), and a deep anesthesia diabetes (DDM) group (n=19). The BIS value was maintained in a range of 50‒59 for the LNDM and LDM groups, and in a range of 40‒49 for the DNDM and DDM groups. Their general information, including anesthesia time, operation time, eye‑opening time after drug withdrawal, the length of post‑anesthesia care unit (PACU) stay, anesthetic dosage, intraoperative fluid replacement volume, intraoperative blood loss, and urine volume were recorded. The incidence of adverse cardiovascular events and the use of vasoactive drugs during surgery were recorded. Blood samples were taken before anesthesia induction and at the end of surgery for determination of serum CGRP and SP by enzyme linked immunosorbent assay (ELISA). Results Compared with the LNDM group, the concentrations of preoperative serum CGRP and SP decreased in the LDM group and the DDM group (P<0.05); the dosage of propofol in the DNDM and DDM groups increased (P<0.05), eye‑opening time was prolonged after drug withdrawal (P<0.05); the concentrations of serum CGRP and SP in the DNDM group, the LDM group, and the DDM group decreased after surgery (P<0.05), the total incidence of intraoperative adverse cardiovascular events in the DDM group increased (P<0.05), and the total use rate of intraoperative vasoactive drugs increased (P<0.05). Compared with the DNDM group, LDM group and DDM group showed decreased concentrations of serum CGRP and SP before and after operation (P<0.05); LDM group showed a decreased amount of propofol (P<0.05), and shortened eye‑opening time after drug withdrawal (P<0.05); the total incidence of intraoperative adverse cardiovascular events in the DDM group increased (P<0.05), and the total use rate of intraoperative vasoactive drugs in the DDM group increased (P<0.05). Compared with the LDM group, the DDM group presented an increased dosage of propofol (P<0.05), prolonged eye‑opening time after drug withdrawal (P<0.05), an increased total incidence of intraoperative adverse cardiovascular events (P<0.05), an increased total use rate of vasoactive drugs (P<0.05), and decreased concentrations of serum CGRP and SP after surgery (P<0.05). Logistic regression analysis showed that serum CGRP [odds ratio (OR)=0.78 (95%CI 0.65, 0.94), P=0.010] and SP [OR=0.98 (95%CI 0.97, 0.10), P=0.020] were the influencing factors of increased adverse cardiovascular events. Conclusions Deep anesthesia is a risk factor of decreased CGRP and SP. Decreases in the concentrations of serum CGRP and SP in diabetic patients are related with deep anesthesia. The increase in the use rate of intraoperative adverse cardiovascular events in diabetic patients is associated with the decrease of serum CGRP and SP.