Abstarct: Chronic non-specific low back pain (CNSLBP) is one of the most prevalent musculoskeletal disorders and a leading cause of disability worldwide. In addition to pain, it is associated with functional impairments, kinesiophobia, alterations in the sensorimotor system, and inflammatory processes. Despite clinical practice guidelines emphasizing multidimensional rehabilitation approaches, evidence regarding their simultaneous effects on functional, psychological, and biological outcomes remains limited. Therefore, the present study aimed to investigate the effects of an eight-week comprehensive exercise rehabilitation program on pain intensity, kinesiophobia, serum levels of IL-1β and IL-8, proprioception, and dynamic balance in men with chronic non-specific low back pain. Methods: This study employed a quasi-experimental pretest–posttest design with a control group and a single-blind outcome assessment. Thirty men aged 20–55 years with chronic non-specific low back pain were randomly allocated to either an exercise group or a control group. The exercise group participated in an eight-week comprehensive exercise rehabilitation program consisting of three sessions per week, whereas the control group received no intervention. Pain intensity, kinesiophobia, proprioception, dynamic balance, and serum levels of IL-1β and IL-8 were assessed before and after the intervention. Data from 24 participants (11 in the exercise group and 13 in the control group) were included in the final analysis. Normally distributed variables were analyzed using analysis of covariance (ANCOVA), whereas non-normally distributed variables were analyzed using the Mann–Whitney U test. Statistical significance was set at P < 0.05. Conclusion: Of the 30 participants initially enrolled, data from 24 participants (11 in the exercise group and 13 in the control group) were included in the final analysis. The eight-week comprehensive exercise rehabilitation program significantly reduced pain intensity (U = 0.500, P = 0.001), decreased serum IL-8 levels (U = 22, Z = −2.879, P = 0.003), improved dynamic balance in the right leg (U = 32, Z = −2.288, P = 0.022) and the left leg (U = 29, Z = −2.462, P = 0.013), and reduced kinesiophobia (F = 5.007, P = 0.036, η² = 0.193) compared with the control group. However, no significant between-group differences were observed in serum IL-1β levels (F = 1.509, P = 0.233, η² = 0.067) or proprioception at 30° (F = 0.588, P = 0.453, η² = 0.027), 60° (F = 0.424, P = 0.522, η² = 0.020), or 90° (F = 3.302, P = 0.144, η² = 0.099).