Objective: To investigate the effects of ultrasound-mediated drug delivery combined with core muscle group training on lumbar spine function, pain intensity, and muscle function in patients with chronic low back pain (CLBP), providing evidence-based support for clinical treatment. Methods: A total of 120 CLBP patients admitted to the Department of Orthopedics in our hospital from January 2023 to December 2024 were selected as research subjects. They were randomly divided into a control group (n = 60) and an observation group (n = 60) using a random number table method. The control group received ultrasound-mediated drug delivery treatment alone, while the observation group received a combination of ultrasound-mediated drug delivery and core muscle group training. Both groups underwent continuous treatment for 8 weeks. The Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), and clinical efficacy were compared between the two groups before treatment, at 4 weeks, and at 8 weeks after treatment. Results: Before treatment, there were no statistically significant differences in VAS scores, ODI, or lumbar spine range of motion between the two groups (p > 0.05). After 4 and 8 weeks of treatment, both groups showed a significant decrease in VAS scores and ODI compared to before treatment (p < 0.05), with the observation group having lower scores than the control group (p < 0.05). The total effective rate in the observation group after 8 weeks of treatment was 93.33% (56/60), which was higher than the 78.33% (47/60) in the control group, with a statistically significant difference (p < 0.05). Conclusion: Ultrasound-mediated drug delivery combined with core muscle group training can effectively alleviate pain intensity, improve lumbar spine function and range of motion, enhance core muscle strength, and demonstrate good safety in CLBP patients. It is worthy of clinical promotion and application.