Background: Local anesthetics are commonly injected into the peribulbar space. However, utilizing solely local anesthetics is linked to delayed initiation of globe akinesia, shorter duration of analgesia, and frequent replenishment with block. This research aimed to evaluate the peribulbar anesthetic effects of neostigmine and dexmedetomidine to those of a local anesthetic combination. Methods: The current study was conducted in Beni-Suef University Hospital on 72 patients. The patients were divided randomly into two equal groups: Dexmedetomidine group included 36 patients who received 50-µg dexmedetomidine added to local anesthetics mixture and neostigmine group included 36 patients who received 0.5 mg of neostigmine added to local anesthetics mixture. Results: There was a significantly longer duration till the onset of block in neostigmine groups than dexmedetomidine group. The initiation of motor and sensory block reached an average of 2.5±0.9 minutes in dexmedetomidine group while in neostigmine group the mean time was 3.9±1.2 minute. Conclusions: This research revealed that adding 50 µg of dexmedetomidine or 0.5 mg of neostigmine to the local anesthetic mix in peribulbar anesthesia for surgery of cataract enhanced the onset of motor and sensory blocks of the globe and prolonged the duration of the block. Dexmedetomidine was better than neostigmine in faster onset of block, prolonged duration, low dose of local anesthetic needed.