Abstract: Complex downhole temperature and pressure loads tend to induce micro-annuli at the casing–cement sheath interface, which can subsequently cause annular pressure and seriously threaten the long-term well bore sealing integrity. Methane-activated self-healing cement offers a highly promising technical solution to this problem. However, a standardized evaluation method for interfacial micro-annulus healing performance that closely matches actual downhole conditions is still lacking. Existing evaluation methods are subject to problems such as small specimen sizes, insufficient capability to simulate downhole temperature and pressure environments, difficulty in standardizing micro-annulus dimensions, and a significant discrepancy between the way defects are prefabricated and the actual micro-annulus generation mechanism. In addition, the processes of fracture creation and healing evaluation are separated from each other, which makes it difficult to conduct in-situ testing under continuous temperature and pressure conditions where the micro-annulus space remains stable. To overcome these limitations, a new physical simulation evaluation method specifically designed for casing–cement sheath interfacial micro-annuli was proposed based on a large-scale physical simulation evaluation platform for cement sheath integrity. The method leveraged the plastic deformation characteristics of cement stone under confining pressure to prefabricate interfacial micro-annuli in situ through cyclic loading, and used the permeability change rate as the quantitative evaluation index, thereby establishing a continuous full-process testing system of “curing—in-situ fracture creation—in-situ healing evaluation”. Laboratory tests showed that this method enabled stable prefabrication of interfacial micro-annuli under different self-healing agent dosages, with excellent repeatability of the critical differential pressure for frcture creation (fluctuation ≤ 2 MPa). The micro-annulus dimension could be controlled within 60 μm by regulating the cyclic loading amplitude, cycle number, and casing pressure, which matches the downhole micro-annulus dimensions (10–46 μm) obtained from field inversion in the Sichuan–Chongqing oil and gas fields. Under constant temperature and pressure conditions, the morphologies of the prefabricated micro-annuli remained stable, and the permeability change only reflected the self-healing effect of the material. The experiments on blank and control samples and multiple parallel repeated experiments further confirmed the reliability of the healing effect evaluation results. This method achieves in-situ interfacial micro-annulus fracture creation on large-scale specimens in the way close to downhole mechanical mechanisms and continuous healing characterization. It can provide an effective technical means for verifying the engineering performance of methane-activated self-healing cement, and also offer methodological reference for large-scale physical simulation evaluation of other self-healing cementing materials.