Under space-based observation conditions, targets are subject to a large number of stars, clutter, false alarms, and other interferences, which can significantly impact the traditional Gaussian mixture probability hypothesis density (GM-PHD) filtering method, leading to tracking biases. To enhance the capability of the traditional GM-PHD method for multi-target tracking in space-based platform observation scenarios, in this article, we propose a GM-PHD algorithm based on spatio-temporal pipeline filtering and enhance the conventional spatio-temporal pipeline filtering method. The proposed algorithm incorporates two key enhancements: firstly, by adaptively adjusting the pipeline’s central position through target state prediction, it ensures continuous target tracking while eliminating noise; secondly, by computing trajectory similarity to distinguish stars from targets, it effectively mitigates stellar interference in target tracking. The proposed algorithm realizes a more accurate estimation of the target by constructing a target state pipeline using the time series and correlating multiple frames of data to achieve a smaller optimal sub-pattern assignment (OSPA) distance and a higher tracking accuracy compared with the traditional algorithm. Through simulations and real-world data validation, the algorithm showcased its capability for multi-target tracking in a space-based context, outperforming traditional methods and effectively addressing the challenge of stellar interference in space-based multi-target tracking.