Background: Chuna manual therapy (CMT), a Korean manual therapy technique predominantly used for treating low back pain (LBP) and related disorders, lacks well-conceived research focusing on its comparative effectiveness, safety, and economic evaluation, particularly with respect to complex CMT with established CMT diagnostic algorithms. This study aims to illustrate a protocol for a randomized clinical study for comparative effectiveness and cost-effectiveness of complex CMT with simple CMT and usual care. Methods: This is a protocol for a three-armed, multicenter, assessor-blinded, pragmatic, randomized controlled trial study. A total of 81 patients suffering from non-acute LBP with pelvic biomechanical lesions (PBL), characterized by a pain duration of at least two weeks and a Numeric Rating Scale (NRS) score of 5 or higher, will be recruited from two Korean medicine hospitals. These participants will be randomly assigned to one of three groups: complex CMT plus usual care (UC; n = 27), simple CMT plus UC (n = 27), or UC groups (n = 27). They will undergo treatment for 4 weeks, and follow-up assessments will be performed 8 weeks after treatment completion. The primary outcome will be the NRS score of LBP, and secondary outcomes will include the Oswestry Disability Index, Patient Global Impression of Change, credibility and expectancy questionnaire, three-dimensional posture analysis indicators, quality of life assessment, economic evaluation, and safety assessments. Discussion: This will be the first study to assess the comparative effectiveness, safety, and cost-effectiveness of complex CMT compared to UC and simple/complex CMT in patients with LBP and PBL. We will also analyze useful diagnostic methods to help in clinical practice for CMT diagnosis.