Tilo (Aishwarya Rai), an immigrant from India, is a shopkeeper, an unusually strong clairvoyant, and a chosen Mistress of Spices. The Spices she gives to her customers help them to satisfy their certain needs and desires, such as "sandalwood to dispel painful memories; black cumin seed to protect against evil eye."

As a young girl, Tilo was initiated as one of several young Mistresses of Spices by the First Mother (Zohra Sehgal), who warns the girls about certain rules they must follow, or face dire consequences. They are instructed never to leave their respective stores all around the world, physically touch the skin of the people they meet, or use the great and incomprehensible strength and power of the Spices to their own ends.

Tilo ends up in the San Francisco Bay Area in a store called "Spice Bazaar". Tilo's customers include Haroun, a cab driver (Nitin Ganatra), a grandfather (Anupam Kher) dealing with an American-born granddaughter Geeta (Padma Lakshmi), Kwesi, a man trying to impress his girlfriend (Adewale Akinnuoye-Agbaje) and Jagjit, a teenager trying to fit in at school (Sonny Gill Dulay).

Her life takes a turn one day, when a young architect named Doug (Dylan McDermott) crashes his motorcycle outside her store. Tilo tends to his injuries while trying to ignore their mutual romantic attraction. Her life changes when he touches her and they begin to fall in love.

But the Spices are displeased, and things soon start to go sour in her relationships with her other customers. Haroun gets in an accident, Geeta's family situation does not improve, Jagjit falls in with the wrong crowd at school, and Kwesi's girlfriend breaks up with him. Doug comes to meet her that night and sadly tells her that his Native American-born mother had died.

Tilo recognizes that the source of these misfortunes is due to her breaking the rules fit for a Mistress. The First Mother comes to her in a vision and scolds her for choosing Doug over the Spices. She vows that she will return to India, and posts a notice about a closing sale. She goes all out to help her customers one last time and tells the Spices that she will spend just one night with Doug, and then she will give herself utterly to them. She closes the store and goes off with Doug for the night. After a night of love-making, she leaves him a note that she must leave and cannot return, but that she will always deeply love him. Then she goes back to the store and sets the Spices on fire, with her at the center of the flames, as a sign of eternal servitude to the mystical Spices.

Doug comes searching for her, and finds the store devastated. But Tilo has not been burned after all; she is still there, alive and barely conscious. There is no sign of a fire, but there has been an earthquake. We see a vision of the First Mother sitting at the beach, telling her that because she demonstrated her willingness to give up everything for the Spices, now she can have everything she desires and the Spices will never desert her again. Doug agrees to help her rebuild the store, and she happily reunites with him as they walk along the beach holding hands.

• Aishwarya Rai Bachchan as Tilo
• Dylan McDermott as Doug
• Ayesha Dharker as Hameeda
• Nitin Ganatra as Haroun
• Sonny Gill Dulay as Jagjit
• Anupam Kher as Geeta's Grandfather
• Adewale Akinnuoye-Agbaje as Kwesi
• Toby Marlow as Young Doug (5-6yrs)
• Caroline Chikezie as Myisha
• Padma Lakshmi as Geeta
• Zohra Sehgal as The First Mother

The film received largely negative reviews from critics. Review aggregator Rotten Tomatoes reports that only 13% of professional critics gave the film a positive review, with an average score of 3.9/10.