The stimulation of tracheal extraction and anesthesia may lead to early postoperative cognitive dysfunction (POCD) in elderly patients, especially within 72 h after surgery, due to the insufficient compensatory and regulatory effects of their cardiovascular system. This study was performed to demonstrate the effects of additional dexmedetomidine (DEX) administration on alleviating early POCD (72 h post intubation) and inflammation in elderly patients who underwent intubation. A parallel-randomized trial was performed in this study. A total of 100 patients aged 60-85 years were randomly divided into two groups (DEX, n = 50; control, n = 50). They received traditional anesthesia and additional DEX medications. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognitive dysfunction of patients. The enzyme-linked immunosorbent assay (ELISA) was used to detect the stress and inflammatory response of the two groups of patients. Administration of DEX significantly improved the MMSE and MoCA scores 24 and 72 h post operation. The S100β and neuron-specific enolase (NSE) levels in serum were downregulated by DEX 6 and 24 h post operation. The norepinephrine and cortisol levels in serum were downregulated by DEX 15 and 30 min post operation. The interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels in serum were also downregulated by DEX 15 and 30 min post operation. DEX alleviated POCD and inflammation in elderly patients who underwent intubation.