Multiple oil-product distribution through a long-distance pipeline to downstream multiple depots is critically important to petroleum refineries and has been extensively studied. Unfortunately, the issues of appropriate handling the trans-mix (TM) between oil-product slugs along the pipeline, as well as the depot inventory management in terms of tank receiving, storage, blending, and discharge operations have not been considered by the previous studies, which could potentially jeopardize their application profitability and operability. Facing these challenges, a general methodology together with a new continuous-time scheduling model have been developed in this paper for simultaneous multi-product pipeline distribution and depot inventory management (MPD-DIM) of a straight pipeline with an input node and multiple output nodes. The scheduling model consists of three sub-models: (i) a preprocessing sub-model for regulating new feeding pipeline slugs; (ii) a TM handling sub-model, and (iii) a product pipeline distribution sub-model with consideration of depot inventory management. Comparably, the development of this study could handle the mixed-interface of oil products appropriately and economically through blending and distillation operations. Meanwhile, the optimization of multi-product pipeline transportation and depot inventory management could be simultaneously accomplished. The efficacy of the developed methodology and MPD-DIM model has been demonstrated by six case studies. © 2020 Elsevier Ltd