Metformin, a first-line antidiabetic agent, has emerged as a promising senotherapeutic agent capable of modulating various senescent-related signaling pathways implicated in aging and age-related diseases. Beyond its glucose-lowering effects, metformin targets several metabolic features of aging, including impaired nutrient sensing, mitochondrial dysfunction, genomic instability, epigenetic alterations, and chronic inflammation as a repurposed conventional drug. Mechanistically, metformin activates AMP-activated protein kinase (AMPK), thereby inhibiting mammalian target of rapamycin (mTOR) signaling, enhancing autophagy, and promoting metabolic resilience. In parallel, it exerts AMPK-independent effects, including inhibiting mitochondrial reactive oxygen species (ROS) formation, suppressing advanced glycation end-products formation, and activating DNA repair mechanisms through the ATM kinase. Metformin also influences the epigenetic landscape by modulating DNA methyltransferases, histone modifiers, and microRNAs. Moreover, it attenuates the detrimental effects of senescence-associated secretory phenotype by inhibiting NF-κB and activating Nrf2-related redox responses. These wide-spectrum effects of metformin make it a potent modulator of cellular senescence and a candidate for delaying the onset of age-related diseases. This chapter provides the signaling mechanisms underlying metformin’s senotherapeutic effects and discusses its potential role in promoting healthy aging and extending healthspan.