Aims Dementia is closely connected with frailty, and these two conditions are common in older adults. However, the biological mechanism that causes frailty in patients with Alzheimer's disease (AD) is not fully understood. We determined whether oxidative stress and inflammatory mechanisms could be associated with physical frailty in patients with AD. Methods We studied 140 elderly outpatients with mild‐to‐moderate AD. Frailty status was determined according to the presence of the following five measurable characteristics: weight loss, exhaustion, low physical activity, slowness and weakness. We measured oxidative stress markers, including plasma levels of diacron reactive oxygen metabolite and biological anti‐oxidant potential, endogenous plasma anti‐oxidants, such as albumin, bilirubin and uric acid, and urinary 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG) and 8‐epiPGF2α (8‐isoprostane), and inflammatory markers, including interleukin‐6 and tumor necrosis factor‐α. Results Among patients, 44 (31%) were non‐frail, 62 (44%) were prefrail and 34 (24%) were frail. Frail and prefrail patients were older, more likely to be women and had more comorbid medical conditions than non‐frail patients. Frail or prefrail patients showed significantly higher diacron reactive oxygen metabolite and lower biological anti‐oxidant potential levels, a significant decrease in bilirubin, a significant increase in urinary 8‐OHdG and 8‐isoprostane levels, and a significantly higher interleukin‐6 level, in contrast to non‐frail patients. Conclusions Physical frailty is common in old and female AD patients with comorbid medical diseases. The present results strongly suggest that oxidative stress and inflammation are involved in the pathophysiology of frailty status in individuals with AD. Geriatr Gerontol Int 2017; 17: 913–918.