Osteoporosis is a major public health problem that can lead to physical disability, working performance limitations, decreased self-sufficiency, and increased hospitalization and mortality rates. People are unaware of osteoporosis, and it is often undiagnosed until fractures occur. Limited studies have been conducted to determine the knowledge, attitude, and practice regarding osteoporosis among middle-aged women in Nepal. This study aimed to determine existing knowledge, attitude, and practice towards osteoporosis among middle and old-aged women in Nepal. A cross-sectional study was conducted among the selected wards of Kirtipur Municipality to recruit 405 participants. Participants were selected using a stratified random sampling technique. Face-to-face interviews using a structured questionnaire were performed to collect the data. Frequencies, percentages, mean, and standard deviation were used to describe the characteristics of participants. Multivariate logistic regression was used to determine the factors associated with knowledge, attitude, and practice regarding osteoporosis. Pearson's correlation coefficient was used to determine the correlation between knowledge, attitude, and practice regarding osteoporosis. The mean ± SD age of the participants was 46.2 ±9.1 years. Nearly half of the participants (48.8%) had good knowledge, while 57.7% and 51.8% had positive attitudes and good practices regarding osteoporosis, respectively. The occupation and income of the participants were statistically significant and associated with the knowledge level. Meanwhile, age, ethnicity, education, occupation, and monthly household income were associated with attitude level. With a good practice level, ethnicity, family type, and education were statistically significant. The knowledge-attitude (rka = 0.093, p < 0.05), attitude-practice (rap = 0.171, p < 0.001), and knowledge-practice (rkp = 0.274, p < 0.001) for osteoporosis were positively correlated. The study found that still around half of the middle and old-aged women had poor knowledge, negative attitudes, and poor practices regarding osteoporosis. Moreover, it highlighted inadequate dietary practices, such as low consumption of milk, vegetables, fruits, and calcium supplements among women, indicates are at greater risk of osteoporosis. The study emphasized the need for community-based awareness programs for the target population such as housemakers, and lower-income groups, to prevent osteoporosis among women.