Objective To investigate the optimal dose of Dexmedetomidine in elderly patients undergoing laparoscopic radical gastrectomy. Methods A total of 75 patients receiving laparoscopic radical gastrectomy received intravenous anesthesia combined with inhalation. Patients were randomly assigned to five groups based on different doses of Dexmedetomidine (n = 15): group A (0.3 μg/kg), group B (0.4 μg/kg), group C (0.5 μg/kg), group D (0.6 μg/ kg) and group E (normal saline group). Basic vital signs were recorded at the three time points in time: entering operating room (T0), the beginning of surgery (T1), and the end of surgery (T2). Blood concentrations of glucose, cortisol, glucagon and adrenaline in the five groups were measured at three time points of T0, T2, and leaving PACU (T3). Time of bronchial catheterization, restlessness score, postoperative analgesic score, Ramsay sedation score and adverse reaction were recorded. Results The levels of MAP and HR in group C and D were lower than those in group E (P < 0.05). The stress indexes and stress responses in group C and group D were significantly decreased than those in group E (P < 0.05). The scores of emergence agitation in group B, C and D were significantly downregulated compared with those in group E (P < 0.05). The postoperative analgesia and sedation score were significantly improved in group B, C and D (P < 0.05). The adverse reactions of group C were significantly diminished than those of other groups (P < 0.05). Conclusions The infusion of Dexmedetomidine 0.5 μg/kg before induction followed by intravenous infusion at a rate of 0.4 μg/(kg·h) is satisfactory to maintain hemodynamic stability and provide good recovery quality in elderly patients receiving laparoscopic radical gastrectomy.