Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance, chronic low-grade inflammation, β-cell dysfunction, oxidative stress, and progressive tissue damage. Emerging evidence highlights microRNAs (miRNAs) as key epigenetic regulators integrating metabolic and inflammatory signaling networks. However, the miRNA-centered mechanisms underlying many traditional antidiabetic medicinal plants remain largely unexplored. This review proposes a systems biology–based, hypothesis-driven framework linking bioactive phytochemicals from five traditional medicinal plants—Urtica dioica (nettle), Eryngium spp. (Boughnagh), Cinnamomum spp. (cinnamon), Silybum marianum (milk thistle), and Citrullus colocynthis (bitter apple)—to microRNA-regulated signaling networks involved in T2DM pathophysiology. A narrative systems biology approach was employed based on integration of phytochemical evidence (polyphenols, flavonoids, lignans, triterpenoids, and saponins) with experimentally validated miRNA–target interactions reported in metabolic, inflammatory, and oxidative stress–related diseases. Indirect mechanistic inference was used to map plant-derived compounds onto key miRNA nodes and downstream signaling pathways. The selected medicinal plants are hypothesized to modulate a convergent set of miRNAs, including miR-155, miR-146a, miR-21, miR-103/107, miR-375, miR-34a, miR-122, and miR-29 family. These miRNAs collectively regulate major signaling axes implicated in T2DM, including NF-κB, PI3K/Akt, AMPK, TGF-β/Smad, and Nrf2/ARE pathways. The integrative network suggests that these phytochemicals may act as multi-target epigenetic modulators rather than single-target agents, potentially restoring metabolic homeostasis and attenuating diabetic complications. This review introduces a hypothesis-driven microRNA-regulated network pharmacology framework for five traditional antidiabetic medicinal plants, providing a conceptual bridge between phytochemistry and systems-level epigenetic regulation in T2DM.