Blind deconvolution of light microscopy images could improve the ability of distinguishing cell-level substances. In this study, we investigated the blind deconvolution framework for a light microscope image, which combines the benefits of bi-l0-l2-norm regularization with compressed sensing and conjugated gradient algorithms. Several existing regularization approaches were limited by staircase artifacts (or cartooned artifacts) and noise amplification. Thus, we implemented our strategy to overcome these problems using the bi-l0-l2-norm regularization proposed. It was investigated through simulations and experiments using optical microscopy images including the background noise. The sharpness was improved through the successful image restoration while minimizing the noise amplification. In addition, quantitative factors of the restored images, including the intensity profile, root-mean-square error (RMSE), edge preservation index (EPI), structural similarity index measure (SSIM), and normalized noise power spectrum, were improved compared to those of existing or comparative images. In particular, the results of using the proposed method showed RMSE, EPI, and SSIM values of approximately 0.12, 0.81, and 0.88 when compared with the reference. In addition, RMSE, EPI, and SSIM values in the restored image were proven to be improved by about 5.97, 1.26, and 1.61 times compared with the degraded image. Consequently, the proposed method is expected to be effective for image restoration and to reduce the cost of a high-performance light microscope.