Mechanistically, EMO inhibited ferroptosis through the GPX4/ACSL4 axis, as evidenced by increased GPX4 and decreased ACSL4 expression.<h4>Conclusions</h4>EMO ameliorates experimental arthritis mainly by suppressing ferroptosis via the GPX4/ACSL4 axis, highlighting ferroptosis as a previously underappreciated therapeutic target in RA and supporting EMO as a potential adjunctive treatment for RA. Here, ACSL4 is linked to rheumatoid arthritis.