| Limnoperna fortunei (golden mussel) is a typical invasive organism. Preventing and controlling L. fortunei is difficult and, at present, the primary means is application of chemicals, resulting in serious secondary pollution of water. Based on our previous study of plant poisons and the physiological and behavioral characteristics of L. fortunei, we found that Nerium indicum (oleander) contained toxic substances that could potentially control L. fortunei with less secondary pollution. In this paper, we compared the effect of oleander extracts on L. fortunei with the effect of chemical reagents, aiming to provide a theoretical basis for controlling L. fortunei with a plant extract. The test L. fortunei were collected in the Yangtze River at Wuhan in September 2016 and divided into four groups according to body length (L≤5 mm, 5 mm25 mm). We first compared the effects of five chemical reagents (glyphosate, tannic acid, sodium hypochlorite, permanganate and chloramine) on L. fortunei and identified the most effective chemical reagents, based on mortality, shell opening rate, adhesion rate and movement. Four concentrations (0 mg/L, 5 mg/L, 50 mg/L, 100 mg/L) of each chemical were used for comparison, and each treatment was run in triplicate with 12 l. fortunei per trial (3 individuals of each body length). The three most effective chemical reagents were permanganate, sodium hypochlorite and chloramine at the highest exposure level (100 mg/L), all three chemicals gave l. fortunei mortality rates > 50%, open shell rates < 30%, adhesion rates < 50%, and no movement. These three chemicals were then compared with oleander extract under the same conditions, based on the same response parameters, using seven concentrations (0 mg/L, 1.0 mg/L, 2.0 mg/L, 4.0 mg/L, 6.0 mg/L and 8.0 mg/L). In all treatments death of L. fortunei occurred after 20 h exposure . The highest mortality of L. fortunei was > 90% in the permanganate and oleander treatments and > 60% in the sodium hypochlorite and chloramine treatments. The optimal concentration of sodium hypochlorite, permanganate, chloramine and oleander extracts were respectively 11 mg/L, 4 mg/L, 4 mg/L, 4 mg/L, and the median lethal times were 111 h, 109 h, 122 h, 82 h.