Research on degenerative spondylolisthesis (DS) has focused primarily on the biomechanical responses of pathological segments, with few studies involving muscle modelling in simulated analysis, leading to an emphasis on the back muscles in physical therapy, neglecting the ventral muscles. The purpose of this study was to quantitatively analyse the biomechanical response of the spinopelvic complex and surrounding muscle groups in DS patients using integrative modelling. The findings may aid in the development of more comprehensive rehabilitation strategies for DS patients. Two new finite element spinopelvic complex models with detailed muscles for normal spine and DS spine (L4 forwards slippage) modelling were established and validated at multiple levels. Then, the spinopelvic position parameters including peak stress of the lumbar isthmic-cortical bone, intervertebral discs, and facet joints; peak strain of the ligaments; peak force of the muscles; and percentage difference in the range of motion were analysed and compared under flexion-extension (F-E), lateral bending (LB), and axial rotation (AR) loading conditions between the two models. Compared with the normal spine model, the DS spine model exhibited greater stress and strain in adjacent biological tissues. Stress at the L4/5 disc and facet joints under AR and LB conditions was approximately 6.6 times greater in the DS spine model than in the normal model, the posterior longitudinal ligament peak strain in the normal model was 1/10 of that in the DS model, and more high-stress areas were found in the DS model, with stress notably transferring forwards. Additionally, compared with the normal spine model, the DS model exhibited greater muscle tensile forces in the lumbosacral muscle groups during F-E and LB motions. The psoas muscle in the DS model was subjected to 23.2% greater tensile force than that in the normal model. These findings indicated that L4 anterior slippage and changes in lumbosacral-pelvic alignment affect the biomechanical response of muscles. In summary, the present work demonstrated a certain level of accuracy and validity of our models as well as the differences between the models. Alterations in spondylolisthesis and the accompanying overall imbalance in the spinopelvic complex result in increased loading response levels of the functional spinal units in DS patients, creating a vicious cycle that exacerbates the imbalance in the lumbosacral region. Therefore, clinicians are encouraged to propose specific exercises for the ventral muscles, such as the psoas group, to address spinopelvic imbalance and halt the progression of DS.