Competitive coexistence of different microorganism species is a fundamental ecological process in the evolution and maintenance of biodiversity. This work studied the interactions happened in the competitive coexistence process of actinomycete Streptomyces sp. and Escherichia coli from morphological and secondary metabolites perspective. We found three important interactions occurred in their successful coexistence process: medium pH was elevated, indole alkaloids with dual inhibiting effects were produced, and culture environment was spatially structured. For the weed-like superior competitor E. coli, its massive growth was suppressed by the elevated pH and the newly produced novel bisindole alkaloid hepchrome. For the inferior Streptomyces sp., its mycelium floated to the medium surface for further colonization, and the growth in liquid medium was inhibited by its self-produced alkaloids such as halichrome A, 1,1,1-Tris (3-indolyl) methane, vibrindole A, and hepchrome. The coexistence of E. coli and Streptomyces sp. was thereby achieved through reduction of spatial and energy resource overlapping and suppression of competition.