Intelligent software systems powered by Large Language Models (LLMs) are increasingly deployed in critical sectors, raising concerns about their safety during runtime. Through an industry-academic collaboration when deploying an LLM-powered virtual customer assistant, a critical software engineering challenge emerged: how to enhance a safer deployment of LLM-powered software systems at runtime? While LlamaGuard, the current state-of-the-art runtime guardrail, offers protection against unsafe inputs, our study reveals a Defense Success Rate (DSR) drop of 24% under obfuscation- and template-based jailbreak attacks. In this paper, we propose DecipherGuard, a novel framework that integrates a deciphering layer to counter obfuscation-based prompts and a low-rank adaptation mechanism to enhance guardrail effectiveness against template-based attacks. Empirical evaluation on over 22,000 prompts demonstrates that DecipherGuard improves DSR by 36% to 65% and Overall Guardrail Performance (OGP) by 20% to 50% compared to LlamaGuard and two other runtime guardrails. These results highlight the effectiveness of DecipherGuard in defending LLM-powered software systems against jailbreak attacks during runtime.