Background: Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease affecting the axial skeleton. For patients with persistent symptoms, biological therapy mainly tumor necrosis factor (TNF) inhibitors and interleukin (IL)-17 inhibitors have proved efficacy in controlling disease progression. However, Peripheral neurological side effects have been reported.  Objective: This work aimed to investigate the effect of biological agents, including anti-TNF-α and anti-IL 17, on peripheral nerves in patients with ankylosing spondylitis (AS). Patients and Methods: This prospective study included 30 biologic-naïve patients with AS, with no neuropathic symptoms or signs. A nerve conduction study (NCS) was performed for each patient at baseline and then after duration of follow-up (12 months). Biological therapy was administered to the patients during this period, including anti-TNF-a agents (5 etanercept, 6 adalimumab, and 5 golimumab) and IL-17 inhibitors (14 secukinumab). Patients were subjected to clinical examination, activity score: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and lab evaluation. NCS was performed where motor and sensory latencies, amplitude, and conduction velocities were recorded and compared before and after treatment. Results: There was a statistically significant increase in motor and sensory latencies in all recorded nerves after treatment, however, these latencies remained within normal physiological ranges. No significant changes were observed in other parameters including amplitude, conduction velocity, or f-waves. Conclusion: It could be concluded that biological therapies, like TNF-α and IL-17 inhibitors, have significantly advanced AS treatment. However, rare neurological side effects, such as demyelinating events, need careful monitoring. Our findings and existing literature highlight the importance of assessing neurological involvement throughout treatment to actively manage adverse effects and improve patient outcomes.