Abstract Peripheral arterial disease (PAD) is a common circulatory condition that leads to reduced blood flow to the limbs, often resulting in limb ischemia which can severely impact a patient’s quality of life and increase the risk of amputation. Early diagnosis and timely intervention are critical in managing PAD-associated limb ischemia. This review provides a comprehensive overview of the latest diagnostic and therapeutic approaches for PAD and limb ischemia. We explored both non-invasive and invasive diagnostic techniques including ankle–brachial index, duplex ultrasonography, magnetic resonance angiography, computed tomography angiography and emerging technologies like molecular imaging and near-infrared spectroscopy. Therapeutic strategies discussed include pharmacological treatments such as antiplatelet agents and statins, endovascular interventions like angioplasty and stenting as well as advanced options such as gene and stem cell therapies. Emerging treatments including non-thermal plasma and extracellular vesicle therapy are also highlighted for their regenerative potential. We have also addressed the challenges of current approaches, including diagnostic limitations, barriers to new therapies and cost considerations aimed at improving outcomes for PAD patients.