Background: Age-related cardiomyocyte vulnerability is driven by a convergent triad of persistent oxidative stress, chronic low-grade inflammation, and senescence-like signaling, which together accelerate functional decline and maladaptive remodeling. Angiotensin II (Ang II), a clinically relevant stress effector, amplifies reactive oxygen species (ROS) production and inflammatory activation, thereby impairing cardiomyocyte survival and repair capacity. Although metformin has emerging cardiovascular benefits beyond glycemic control, its coordinated capacity to counteract Ang II-driven inflammaging-like injury through the coupled regulation of antioxidant and anti-inflammatory pathways in human cardiomyocytes remains insufficiently defined. Objectives: This study aimed to determine whether metformin attenuates Ang II-induced injury and impaired repair in human AC16 cardiomyocytes and to evaluate whether this protection is associated with coordinated activation of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) and suppression of Nuclear Factor-κB (NF-κB). Methods: Human AC16 cardiomyocytes were preconditioned with metformin (0.5 or 1.0 mM) for 2 h and then challenged with Ang II (0.1 - 2.0 μM) under continuous metformin exposure. The primary efficacy endpoints were cell survival, quantified using the MTT assay, and repair competence, assessed by scratch wound closure. Secondary mechanistic endpoints included inflammatory mediators (TNFA, IL6, and IL1B); senescence-associated markers (CDKN2A/p16 and CDKN1A/p21); antioxidant genes linked to Nrf2 signaling (NFE2L2/Nrf2, HMOX1/HO-1, and NQO1); NF-κB pathway activation; antioxidant and apoptosis-related proteins; Nrf2 compartmentalization; and intracellular ROS. Results: Angiotensin II induced a dose-dependent injury phenotype in AC16 cardiomyocytes, reducing viability from 100.0 ± 1.1% in control cells to 64.9 ± 1.6% at 1.0 μM and 53.0 ± 1.6% at 2.0 μM, while markedly impairing wound closure (80.0 ± 2.0% in control vs 32.3 ± 2.5% with Ang II). Metformin attenuated this injury in a concentration-dependent manner, restoring viability to 81.7 ± 1.0% with 0.5 mM and 89.7 ± 1.0% with 1.0 mM and improving wound closure to 52.3 ± 2.5% and 70.0 ± 2.0%, respectively. Angiotensin II also robustly increased inflammatory cytokine expression, with TNFA, IL6, and IL1B increasing to 27.86 ± 2.79-fold, 29.86 ± 2.99-fold, and 29.86 ± 2.99-fold, respectively, accompanied by NF-κB activation, ROS accumulation (187.7 ± 2.5% of control), apoptosis-associated signaling, and upregulation of the senescence-like markers p16 and p21. Metformin markedly suppressed these responses, reducing cytokine expression toward near-baseline levels, lowering ROS to 120.0 ± 2.0%, decreasing the BAX/BCL-2 ratio from 2.98 to 1.19, and reducing cleaved caspase-3 and cleaved PARP to 120% and 112% of control, respectively. In parallel, metformin enhanced Nrf2-associated antioxidant signaling, increasing NFE2L2 to 2.14 ± 0.17-fold, HMOX1 to 4.29 ± 0.30-fold, and NQO1 to 3.81 ± 0.27-fold, consistent with enhanced antioxidant defense under Ang II stress. Conclusions: Metformin attenuated Ang II-driven cardiac inflammaging-like injury and impaired repair, in association with reduced inflammatory signaling and enhanced activation of antioxidant pathways. These findings support a mechanistically coherent model in which NF-κB suppression and Nrf2 activation may contribute to metformin-mediated protection; however, direct pathway dependence requires confirmation through perturbation-based studies.