Abstract: Aiming at the technical challenges encountered in drilling the horizontal wells with extremely narrow cluster spacing (1–5 m) in the low-maturity Chang 7₃ shale oil reservoirs of Zhengning Block in Ordos Basin—namely wellbore instability and lost circulation triggered by high illite/smectite mixed-layer content, well-developed microfractures and low compressive strength of target reservoirs—a water-based anti-sloughing drilling fluid system designated CQ-Seal was developed. This system adopts self-developed micro-nano plugging agents and inhibitors for drilling fluids, with plugging formulation optimized via Box-Behnken response surface methodology experiments. Laboratory evaluations were conducted to characterize its plugging capacity, inhibition performance, and effect on the compressive strength of rock core samples.Test results demonstrate that the CQ-Seal water-based drilling fluid achieves a cuttings recovery rate of 96.3%, a shale swelling rate as low as 1.7%, and a reduction in rock core compressive strength of less than 10% after immersion. Field applications were carried out across five horizontal wells within Zheng 75 horizontal well cluster. The drilling fluid density was reduced to 1.13–1.30 g/cm³, the hole enlargement ratio was merely 5.4%–6.3%, the average drilling cycle reached 16.56 days, and the casing run-in success rate in one attempt hit 100%.By synergistically enhancing nanoscale physical plugging and organic potassium salt inhibition, the CQ-Seal system substantially improves wellbore stability for shale oil well clusters with ultra-narrow spacing, delivering technical support for the efficient development of low-maturity shale oil resources.