A French Jew and colonel and chief intelligence officer in the French army that works with the Qing Bang. Although he has mastered Hokuto Sonkaken, he prefers using conventional fighting methods like guns and swords, irritating even the likes of Mang Kuang-Yun at one point. He has a sister, Sophie, who suffered trauma resulting in memory suppression due to her experiences in escaping from Nazi Germany as her husband (a non-Jewish German who was prohibited from marrying her by Nazi law) got sent to a concentration camp. When she regained her memory by Kenshiro's acupressure, she was assassinated by Zhang Tai-Yan. De Guise was eventually wounded fatally by Liú Fēi-Yàn when the latter deemed him unfit to take care of Erika Arendt and challenged him to a duel. Kenshiro used acupressure techniques on him to prolong his life just long enough to watch his friends staging a glimpse of his vision -- a Shanghai in prosperity (where Jews can take refuge). Believing that Kenshiro and friends will make it come true, he then died in peace.
- Charles de Guise bears several similarities to Rei from Hokuto no Ken. Both bear villanous appearances when they first appear but are soon revealed to be on the good side as well as crucial allies to the main character. Both have younger sisters who suffer from disorders and both die after their lives are briefly extended.