Set in the Republic era, All That Is Bitter Is Sweet follows Dou Gaai Kei (Linda Chung), the only daughter of the wealthy Dou family of Foshan. As the daughter of the biggest pharmaceutical seller in the city, Gaai Kei has a keen interest in medicine, but her father refuses to see her as his successor, simply because shes a woman.
Just as Gaai Kei is about to marry Chong Gai Zou (Raymond Wong), the mayors son, a virulent epidemic starts to spread through the city. The disease eventually claims Gai Zous life & causes Gaai Keis father to be imprisoned, leaving Gaai Kei penniless & alone. As Gaai Kei is unable to keep the pharmacy running, terminally ill merchant Ding Yat Yuen (Ruco Chan) decides to buy it. Desperate to keep her fathers legacy, Gaai Kei offers to treat Yat Yuens illness in exchange for him keeping the pharmacy & not reselling it for profit. As the days go by, the studious & intelligent Gaai Kei learns more & more about medicine, & through spending time together, she & Yat Yuen start to fall for one another. At this time, Gai Zous twin brother Gai Zong (also Raymond Wong) returns to Foshan, & he has long harbored feelings for Gaai Kei...