Background: Ultrasound-guided sciatic and femoral nerve blocks are widely used for below-knee surgeries, with adjuvants often added to local anesthetics to improve block efficacy and duration. Ketamine and dexmedetomidine are two commonly used adjuvants with distinct mechanisms and clinical profiles. Objective: This study aimed to compare the efficacy and safety of ketamine and dexmedetomidine as additives to bupivacaine in ultrasound-guided combined sciatic and femoral nerve blocks for below-knee surgeries. Patients and methods: This study involved 80 patients aged 18–60 years (ASA grade I–II) who were scheduled for below-knee surgeries. Patients were randomly assigned to receive a combination of 40 mL of 0.5% bupivacaine with either 0.5 mg/kg ketamine (Group K) or 50 µg/kg dexmedetomidine (Group D). The measured outcomes included the onset and duration of sensory and motor blockade, pain scores (VAS), hemodynamic parameters, and adverse effects. Results: A total of 80 patients were enrolled, with no significant differences in demographic characteristics between group K and group D groups. Heart rate and mean arterial blood pressure remained stable, with no significant intergroup differences. Sensory block duration was significantly longer in group K (14.21 ± 0.35 hours) than in group D (13.94 ± 0.29 hours) (p = 0.0003), while motor block duration was similar (13.81 ± 1.46 vs. 13.3 ± 0.9 hours, p = 0.064). VAS scores showed no significant differences at any time point (p > 0.05). Sedation levels were significantly higher in group D, with scores of 2.5 ± 0.03 vs. 2 ± 0.02 at 15 minutes (p < 0.001), maintaining significance up to 6 hours. Bradycardia was more frequent in Group D (20% vs. 5%, p = 0.043), while other adverse events, including hypotension (30% vs. 20%, p = 0.302), vomiting (12.5% vs. 5%, p = 0.235), and agitation (10% vs. 2.5%, p = 0.166), were comparable between groups. Conclusion: Both ketamine and dexmedetomidine effectively prolonged sensory and motor block durations, with ketamine providing a longer sensory block and dexmedetomidine inducing deeper sedation but a higher incidence of bradycardia.