The process of printing defect detection usually suffers from challenges such as inaccurate defect extraction and localization, caused by uneven illumination and complex textures. Moreover, image difference-based defect detection methods often result in numerous small-scale pseudo defects. To address these challenges, this paper proposes a comprehensive defect detection approach that integrates brightness correction and a two-stage defect detection strategy for self-adhesive printed materials. Concretely, a joint bilateral filter coupled with brightness correction corrects uneven brightness properly, meanwhile smoothing the grid-like texture in complex printed material images. Then, in the first detection stage, an image difference method based on a bright–dark difference template group is designed to effectively locate printing defects despite slight brightness fluctuations. Afterward, a discriminative method based on feature similarity is employed to filter out small-scale pseudo-defects in the second detection stage. The experimental results show that the improved difference method achieves an average precision of 99.1% in defect localization on five different printing pattern samples. Furthermore, the second stage reduces the false detection rate to under 0.5% while maintaining the low missed rate.