Background Total intravenous anesthesia (TIVA) is a well-documented anesthetic concept for some animal species, including dogs and horses; however, information about TIVA protocols in goats is currently inadequate. Therefore, this study aimed to compare the clinicophysiological and hematobiochemical effects of dexmedetomidine (DEX) and diazepam premedication with ketamine and propofol. Result The DEX-treated group showed a significantly decreased heart rate compared with the diazepam-treated group. Onset of anesthesia and sedation in group I was significantly faster than that in group II (0.33 ± 0.08 and 0.25 ± 0.08 min vs. 3.33 ± 1.53 and 2.0 ± 1.0 min, respectively). Duration of anesthesia and sedation in group I was significantly longer than that in group II (66.67 ± 7.64 and 161.3 ± 43.3 min vs. 37.0 ± 5.19 and 60.33 ± 7.57 min, respectively). The total recovery period in group II was significantly shorter than that in group I (47.0 ± 7.21 vs. 98.33 ± 15.27 min). Smooth induction and recovery occurred in all goats in group I, whereas most goats in group II exhibited slightly prolonged induction with mild excitation and presence of swallowing reflex and prolonged struggling during recovery. Conclusion In TIVA, premedication with DEX produces excellent quality anesthesia, analgesia, sedation, and muscle relaxation. Furthermore, it produces a longer duration of anesthesia, sedation, and analgesia than premedication with diazepam. For these reasons, DEX is more suitable for long surgical procedures, whereas diazepam can be used in minor surgical procedures in goats. Both drug combinations produce hemodynamic stability.