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Abstract Purpose This study aims to assess the effectiveness of Percutaneous Endoscopic Posterior Lumbar Interbody Fusion (PE-PLIF) combined with a novel Unilateral Laminotomy for Bilateral Decompression (ULBD) approach using a large-channel endoscope in treating Lumbar Degenerative Diseases (LDD). Methods This retrospective analysis evaluates 41 LDD patients treated with PE-PLIF and ULBD from January 2021 to June 2023. A novel ULBD approach, called ‘Non-touch Over-Top’ technique, was utilized in this study. We compared preoperative and postoperative metrics such as demographic data, Visual Analogue Scale (VAS) for pain, Oswestry Disability Index (ODI), Japanese Orthopedic Association (JOA) score, surgical details, and radiographic changes. Results The average follow-up duration was 14.41 ± 2.86 months. Notable improvements were observed postoperatively in VAS scores for back and leg pain (from 5.56 ± 0.20 and 6.95 ± 0.24 to 0.20 ± 0.06 and 0.12 ± 0.05), ODI (from 58.68 ± 0.80% to 8.10 ± 0.49%), and JOA scores (from 9.37 ± 0.37 to 25.07 ± 0.38). Radiographic measurements showed significant improvements in lumbar and segmental lordosis angles, disc height, and spinal canal area. A high fusion rate (97.56% at 6 months, 100% at 12 months) and a low cage subsidence rate (2.44%) were noted. Conclusions PE-PLIF combined with the novel ULBD technique via a large-channel endoscope offers significant short-term benefits for LDD management. The procedure effectively expands spinal canal volume, decompresses nerve structures, improves lumbar alignment, and stabilizes the spine. Notably, it improves patients' quality of life and minimizes complications, highlighting its potential as a promising LDD treatment option.