Background Lumbosacral radiculopathy (LSR) due to lumbar disc herniation (LDH) is a condition caused by mechanical compression of nerve roots. Various physical therapy interventions have been proposed for the conservative management of LSR due to LDH. However, the study of physical therapy interventions in a multimodal form is lacking. Additionally, the effect of physical therapy on diffusion tensor imaging (DTI) parameters of the compressed nerve root has not been studied. This study aimed to investigate the effects of multimodal physical therapy (MPT) on pain, disability, soleus H-reflex, and DTI parameters of the compressed nerve root in patients with chronic unilateral LSR due to LDH. Methods A prospective preliminary pre-post clinical trial with a convenience sample was conducted. A total of 14 patients with chronic unilateral LSR due to paracentral L4-L5 or L5-S1 LDH were recruited for the study. Participants received a total of 18 sessions of a six-week MPT program that consisted of electrophysical agents, manual therapy interventions, and core stability exercises. Electrophysical agents involved interferential current and hot pack. Manual therapy interventions included myofascial release, side posture positional distraction, passive spinal rotation mobilization, and high-velocity low-amplitude manipulation. Visual analog scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), soleus H-reflex amplitude, side-to-side amplitude (H/H) ratio, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) of the compressed nerve root were measured at baseline and post-intervention. Results There were significant improvements in VAS, RMDQ, H/H ratio, FA, and ADC of the compressed nerve root. Furthermore, significant improvement was found in the affected side compared with the contralateral side in H-reflex amplitude. Conclusions The observations of this preliminary trial suggest that MPT is a successful intervention in patients with chronic unilateral LSR due to LDH. Regarding DTI parameters of the compressed nerve root, FA increased and ADC decreased. Future studies with a control group, large sample sizes, and longer follow-up periods are needed.