战乱时期，江湖上五大毒宗拔地而起，五大毒宗对应着生活中的五毒。圣鳞教教主南宫懿为满足自己私心，抢夺各门派武功秘籍。一个毫无征兆的夜晚，狂风四起。天龙门掌门失踪，金乌派惨遭灭门，天蟾谷一夜间彻底消失。天蟾谷掌门幼子独孤俞在被追杀的过程中被谷中长老独孤仲使出蛤蟆神功所救，并由一农村老妇抚养，是为奶奶。十八年后。独孤俞结识了南宫翎，两人互生情愫，却没想到是大仇人南宫懿的女儿，而南宫懿十八年来一直在寻找独孤俞。独孤俞被抓，翎翎冒死救出，一次意外独孤俞坠崖练成了蛤蟆神功。独孤俞前去找南宫懿报仇，南宫翎为了终止这场大战牺牲了自己，南宫懿亲手杀死了自己最爱的女儿，走火入魔，成了疯子。最终独孤俞也放下了恩怨。
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