Glutaminolysis inhibitors have shown early promise in cancer therapeutics. Specifically, kidney-type glutaminase (KGA) has been a long-standing anti-tumor drug target; KGA allosteric inhibitors have attracted great attention due to their superior enzyme specificity and good drug safety profiles. However, the main issue with allosteric inhibitors—including BPTES, CB-839, and the recently developed KGA allosteric and glutamate dehydrogenase (GDH) dual inhibitor, Hexylselen (CPD-3B)—is their low solubility; it leads to limited in vivo efficacy. To optimize their formulation, various delivery carriers were screened in the present study. Soluplus® (SOL), an amphiphilic graft polymer, showed an interesting structure–solubility/activity relationship with Selen molecules containing different middle chain sizes. Among these molecules, the long chain molecule CPD-3B showed 3000-fold increased solubility with SOL, forming well-dispersed and stable micelles 60–80 nm in size. Moreover, CPD-3B@SOL micelles exhibited good metabolic stability in both blood and liver microsomes. These advantages significantly enhanced the bioavailability and in vivo antitumor efficacy of CPD-3B@SOL micelles in the H22 hepatocarcinoma xenograft mouse model. Thus, the current study provided a practical delivery system for allosteric inhibitors of glutaminase, which is one of the bottlenecks of targeting tumor glutaminolysis.