Iron deficiency anemia affects approximately 1.62 billion people worldwide, yet traditional iron supplements present bioavailability limitations and gastrointestinal side effects. This randomized, double-blind clinical trial investigated a novel Auricularia auricula polysaccharide-iron complex (AAPIC) compared with heme iron and ferrous glycinate in 180 iron-deficient adults receiving 30 mg elemental iron daily for 12 weeks. AAPIC achieved comparable hemoglobin improvements (from 98.3 ± 8.7 to 126.5 ± 9.2 g/L) to heme iron (from 97.8 ± 9.1 to 128.3 ± 8.6 g/L) and was significantly superior to ferrous glycinate (from 98.6 ± 8.9 to 119.7 ± 10.3 g/L; p < 0.001). Iron absorption efficiency showed AAPIC at 23.7 ± 4.2%, heme iron at 25.1 ± 3.8%, and ferrous glycinate at 18.4 ± 5.1%. Toxicological assessments revealed no hepatotoxicity, nephrotoxicity, or mutagenicity. Gastrointestinal adverse events occurred in 8.3% of AAPIC recipients versus 15.0% with ferrous glycinate and 10.0% with heme iron. The polysaccharide component facilitates iron transport through enhanced intestinal uptake mechanisms. AAPIC represents a promising, well-tolerated alternative with clinical efficacy comparable to established iron formulations.