A series of ascaridole derivatives 1-10 were successfully synthesized and their structures were characterized by 1 H, 13C NMR and high-resolution mass spectroscopy. The nematocidal activities of these compounds were evaluated and the results indicated that these derivatives have better nematocidal activities against Meloidogyne incognita than Aphelenchoides besseyi. Interestingly, cis-isomers of Z-3,6-epidioxy-1-methyl-4-isopropylcyclohexene (2) and Z-3,6-epidioxy-1-methyl-4-isopropenylcyclohexene (4) are more active than their corresponding trans-isomers. Among them, 1,4-epidioxy-4-isopropyl-2-cyclohexenoic acid (8) and 1,4-epidioxy-4-isopropyl-2-cyclohexenecarboxylic acid methyl ester (10) exhibited significant higher nematocidal activities than those of other analogs; therefore the carboxylic acid or carboxyl ester substituent on the ring might be essential for high nematocidal activity. Compared with the toxicity of a commercial nematocide, Oxamyl, these derivatives can be considered effective and promising.