Mesoporous metal-organic networks have attracted widespread interest owing to their potential applications in diverse fields including gas storage, separations, catalysis, and drug delivery. Despite recent advances, the synthesis of metal-organic networks with large and ordered mesochannels (>20 nm), which are important for loading, separating, and releasing macromolecules, remains a challenge. Herein, we report a templating strategy using sacrificial double cubic network polymer cubosomes (Im (3) over barm) to synthesize ordered mesoporous metal-phenolic particles (meso-MPN particles) with a large-pore (similar to 40 nm) single cubic network (Pm (3) over barm). We demonstrate that the large-pore network and the phenolic groups in the mesoMPN particles enable high loadings of various proteins (e.g., horseradish peroxidase (HRP), bovine hemoglobin, immunoglobulin G, and glucose oxidase (GOx)), which have different shapes, charges, and sizes (i.e., molecular weights spanning 44-160 kDa). For example, GOx loading in the meso-MPN particles was 362 mg g(-1), which is similar to 6-fold higher than the amount loaded in commercially available SiO2 particles with an average pore size of SO nm. Furthermore, we show that HRP, when loaded in the meso-MPN particles (486 mg g(-1)), retained similar to 82% activity of free HRP in solution and can be recycled at least five times with a minimal (similar to 13%) decrease in HRP activity, which exceeds HRP performance in SO nm pore SiO2 particles (similar to 36% retained activity and similar to 30% activity loss when recycled five times). Considering the wide selection of naturally abundant polyphenols (>8000 species) and metal ions available, the present cubosome-enabled strategy is expected to provide new avenues for designing a range of meso-MPN particles for various applications.