Objective In order to meet the specific requirements of drug defect detection system, there is a need to have a better image segmentation result. Methods On the basis of two-dimensional Otsu method, a new threshold segmentation output function was proposed by improving the traditional algorithm, which significantly lowered the computational complexity. Results Theoretical analysis and simulation results showed that this new method could cover the drug image edge details, had improved segmentation accuracy, and the speed of segmentation met the requirement of real-time detection. Conclusion The improved algorithm has applicability and real-time performance in defect detection of aluminium-plastic drug packaging.