Molly (Kate Hudson) and Carl (Matt Dillon) are excitedly preparing for their wedding day in beautiful Hawaii. However, their plans take an unexpected turn when Carl's friend Dupree (Owen Wilson) goes missing, prompting Carl and his buddy Neil (Seth Rogen) to embark on a quest to find him. Their search leads them to Dupree, who comically hitched a ride with a light plane after mistakenly landing on the wrong island. As the wedding approaches, tensions arise when Molly's father, Thompson (Michael Douglas), who also happens to be the CEO of the company where Carl works, makes a toast that pokes fun at Carl, hinting at future conflicts.
Later, during a pre-celebration at a bar, Carl prioritizes Molly over Dupree, leading to some tensions. On the beach, the friends mend their bond as Dupree apologizes for his previous behavior, acknowledging Carl's unique qualities, which he playfully dubs "Carlness." Following their wedding, Carl is surprised to learn that he has been promoted by Mr. Thompson, albeit with some unusual and absurd adjustments to his proposed architecture project.
As it turns out, Thompson’s requests grow increasingly bizarre, including a demand for Carl to take on the Thompson name and undergo a vasectomy. Before Carl heads home to celebrate with Molly, he encounters Dupree, who reveals he has been fired and evicted, leading Carl to invite him to stay temporarily. Although Molly tries to be accommodating, Dupree's presence brings chaos and messiness into their home.
In a heartfelt attempt to help Dupree, Molly sets him up with a woman from her job, a Mormon librarian. However, when she returns home one day, she is shocked to find romantic candles lighting up her living room, signaling Dupree’s failed attempt at romance that results in his eviction once again.
As Carl struggles with the mounting pressure at work, he and Molly still carve out some time for dinner. Yet, when they return home, they find Dupree soaked and struggling with his belongings in the rain, leading Molly to insist they bring him back into their home, albeit with Carl voicing that Dupree needs to improve his behavior.
The next day, Dupree tries to make amends by redecorating their living room and assisting with thank-you letters, while also befriending kids from the neighborhood. Carl even invites him to career day at Molly's school, but when Dupree cooks dinner for Molly and Carl arrives late, it sparks jealousy and a fight between the two friends.
Feeling betrayed, Carl kicks Dupree out, which deeply shocks Dupree. During a dinner that includes Mr. Thompson, Dupree sneaks in to retrieve his belongings and, in a humorous twist, ends up falling from the roof. Mr. Thompson surprisingly takes a shine to Dupree, further aggravating Carl. This leads to an explosive confrontation where Carl’s frustrations boil over.
Subsequently, after a hospital visit and wearing a neck brace, Dupree and Molly confront Mr. Thompson about his real feelings toward Carl. Meanwhile, Carl has left the scene, and tensions remain high. Through a series of chaotic events, Dupree locates Carl and encourages him to confront Molly directly, leading to a heartfelt reconciliation.
In the end, Dupree turns his life around, becoming an author and motivational speaker, all while fostering a unique partnership with Paco, the security guard, who becomes his right-hand man. Their wild journey blends mishaps, humor, and emotional growth, culminating in a beautifully chaotic narrative about friendship and commitment.
