Background: Failed back surgery syndrome is a common problem faced by chronic pain management specialists. Steroid-only epidural injections have modest efficacy because of excessive scarring. Epidural hyaluronidase (HA), functions as a depolymerizing agent, successfully breaking down adhesions and collagen bundles, whereas dexmedetomidine (DEX) helps to reduce inflammation. Methods: The current study is a randomized, double blind, clinical trial. The study cohort included population with persistent (> 6 months) back and/or radicular lower limb pain after laminectomy. Group I (HA group) received bupivacaine 0.5% (5 mg), triamcinolone 40 mg, sterile saline (2 ml), and HA (1500 IU) instilled in 1 mL of distilled water. Group II (DEX group) received bupivacaine 0.5% (5 mg), triamcinolone 40 mg (1 ml), DEX (0.5 mcg/kg), and sterile saline (2 ml). Results: Both groups showed significant reductions in VAS scores at all follow-ups compared to the pre-injection values. At 6 months, the DEX group experienced a significantly greater reduction in pain scores than the HA group (P = 0.003). In terms of the MODI, both groups showed significant reductions in disability scores at all follow-ups relative to the pre-injection values. The DEX group showed greater improvement in MODI values than the HA group. No significant complications were reported. Conclusions Both DEX and HA yielded significant improvements in pain and disability scores compared with pre-injection levels. The DEX group showed a more substantial and long-term reduction in both pain scores and disability index than the HA group.