This paper introduces MetaDefense, a novel framework for defending against finetuning-based jailbreak attacks in large language models (LLMs). We observe that existing defense mechanisms fail to generalize to harmful queries disguised by unseen attack templates, despite LLMs being capable of distinguishing disguised harmful queries in the embedding space. Based on these insights, we propose a two-stage defense approach: (i) pre-generation defense that detects harmful queries before response generation begins, and (ii) mid-generation defense that monitors partial responses during generation to prevent outputting more harmful content. Our MetaDefense trains the LLM to predict the harmfulness of both queries and partial responses using specialized prompts, enabling early termination of potentially harmful interactions. Extensive experiments across multiple LLM architectures (LLaMA-2-7B, Qwen-2.5-3B-Instruct, and LLaMA-3.2-3B-Instruct) demonstrate that MetaDefense significantly outperforms existing defense mechanisms, achieving robust defense against harmful queries with seen and unseen attack templates while maintaining competitive performance on benign tasks. Code is available at https://github.com/ws-jiang/MetaDefense.