Different factors, such as inflammation, oxidative stress, extracellular matrix degradation and apoptosis, affect the pathophysiology of chronic obstructive pulmonary disease (COPD), as a progressive disease characterised by permanent airflow limitation. Herbal supplements with anti-inflammatory and antioxidant properties can help treat certain chronic diseases. The current study aimed at investigating the preventive effects of crocin supplementation on the serum concentrations of IL-6, TNF-α, exercise capacity and pulmonary function tests (PFT) in patients with COPD. The present prospective randomised clinical trial equally divided fifty-seven patients with COPD into a placebo and an intervention group, who respectively received a placebo and crocin (15 mg twice day for 12 weeks) as a supplement. ELISA was used to measure serum levels of IL-6 and TNF-α, also PFT and exercise capacity based on 6-min walking distance test (6MWD), which was performed at the beginning and end of the study. Crocin improved the results of PFT (P < 0·05) and 6-MWD (P < 0·001) and exerted preventive effects by increasing the serum levels of IL-6 in patients with COPD compared with those in the placebo group (P < 0·05). Intervention with crocin significantly lowered serum levels of TNF-α at the end of the study (P < 0·01). The present findings suggest crocin supplementation improves exercise capacity and PFT in patients with COPD by reducing serum levels of inflammatory factors.